Cancer Genetics and Cytogenetics via MedWorm.com

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Erratum: Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

Oliver A. Hampton, Maxim Koriabine, Christopher A. Miller, Cristian Coarfa, Jian Li, Petra Den Hollander, Caroline Schoenherr, Lucia Carbone, Mikhail Nefedov, Boudewijn F.H. Ten Hallers, Adrian V. Lee, Pieter J. De Jong, Aleksandar Milosavljevic. Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines. Cancer Genetics 2011;204:447–457. (Source: Cancer Genetics and Cytogenetics)

Sequential transient novel chromosomal translocations in a patient with chronic myelogenous leukemia in complete cytogenetic remission after therapy with imatinib mesylate

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

Imatinib mesylate (IM) is the first tyrosine kinase inhibitor (TKI) introduced for the treatment of chronic myelogenous leukemia (CML) with remarkable high rates of complete hematologic and cytogenetic response and an acceptable safety and toxicity profile. Clonal aberrations (CAs) in Philadelphia (Ph)-chromosome negative metaphases have been reported in patients with CML after treatment with IM, with a varying frequency between series (1.6–20.6%) . Most CAs are numerical aberrations, whereas structural aberrations, in particular, balanced translocations are much less frequent . (Source: Cancer Genetics and Cytogenetics)

A possible 5′-NRIP1/UHRF1-3′ fusion gene detected by array CGH analysis in a Ph+ ALL patient

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

A translocation between chromosomes 19 and 21 [dic/t(19;21)(p13;v)] is very rare. To date, only three cases of this particular chromosomal abnormality have been reported. The translocations in these three cases were secondary changes in acute lymphoblastic leukemia (ALL) patients with the t(9;22) translocation. The gene(s) at the breakpoints of either chromosome 19p13 or 21q have not yet been identified. Here, we present a case study of a 21-year-old female with a diagnosis of precursor B cell ALL, with the t(9;22) translocation and secondary changes including a der(19)t(19;21) and an extra Philadelphia (Ph+) chromosome [der(22)t(9;22)]. Array comparative genomic hybridization (aCGH) analysis identified UHRF1 and NRIP1 as genes that were interrupted at the breakpoints of 19p13.3 and 21q21....

Single nucleotide polymorphism array-based karyotyping shows sequential genomic changes from monosomy to copy-neutral loss of heterozygosity of chromosome 7 and 20q deletion within a balanced translocation t(14;20) in AML

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

We report serial genetic studies on a patient diagnosed with chronic myelomonocytic leukemia who progressed to acute leukemia. Monosomy 7 was predominantly found at diagnosis, but clones changed to CN-LOH of chromosome 7 with disease progression. Furthermore, subclones with genomic aberrations of 3q gain, 1p CN-LOH, and trisomy 12 newly appeared, suggesting that they were also involved in the transformation process. Additionally, by SNP-A, a presumably balanced translocation, t(14;20), identified by metaphase cytogenetics, was shown to result in an unbalanced 20q deletion at the breakpoint. The sequential changes identified by SNP-A may provide a better understanding of the mechanism of clonal evolution. (Source: Cancer Genetics and Cytogenetics)

Similar cytogenetic findings in two synchronous secondary peripheral chondrosarcomas in a patient with multiple osteochondromas

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

We describe the genetic examination of three secondary peripheral chondrosarcomas that had arisen synchronously from osteochondromas in a patient with MO by chromosome banding, high resolution chromosomal comparative genomic hybridization, and mutation analysis of the EXT1 and EXT2 genes. In two of the tumors (the third was not genetically informative), very similar chromosome abnormalities were found, indicating that they must somehow be part of the same neoplastic process in spite of being anatomically distinct. (Source: Cancer Genetics and Cytogenetics)

Molecular cytogenetic characterization of epithelioid hemangioendothelioma

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

In this study, 14 cases of EHE were investigated by interphase fluorescence in situ hybridization (FISH) directed against the translocation breakpoint 1p36.3. A subset of cases was also analyzed by comparative genomic hybridization (CGH) and image cytometry. Five out of eight cases that could be successfully analyzed by FISH harbored a chromosomal break in the 1p36.3 region. The break-apart signals were present in diploid nuclei, and less frequently also in tetraploid nuclei. In the latter, the chromosomal break was present twice, suggesting that polyploidy occurred after the chromosomal alteration. DNA cytometry confirmed that tetraploid cells were present in most examined cases with one case indicating almost equal amounts of diploid and tetraploid tumor cells. CGH revealed single chromo...

A t(1;9)(q10;q10) translocation with additional 6q23 and 9q22 rearrangements in a case of chondromyxoid fibroma

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

Chondromyxoid fibroma (CMF) is a rare cartilaginous tumor of bone. It typically presents in the long tubular bones and to a lesser extent in the small bones of the hands and feet of young adults. To date, several cytogenetic abnormalities have been described in association with CMF. We studied a phalangeal CMF from a 13-year-old female by cytogenetic methods. We found a novel unbalanced translocation between the long arms of chromosomes 1 and 9, resulting in loss of 1p. In addition, rearrangements involving the 6q23 and 9q22 regions were also observed. To our knowledge, this is the first report in the literature describing this novel chromosomal translocation in CMF. (Source: Cancer Genetics and Cytogenetics)

Clonal diversity analysis using SNP microarray: a new prognostic tool for chronic lymphocytic leukemia

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

In conclusion, SNP microarray studies with simultaneous evaluation of genomic alterations and mosaic distribution of clones can be used to assess apparent clonal evolution via analysis of clonal diversity. Since clonal evolution in CLL is strongly correlated with disease progression, whole genome SNP microarray analysis provides a new comprehensive and reliable prognostic tool for CLL patients. (Source: Cancer Genetics and Cytogenetics)

Two novel unbalanced whole arm translocations are frequently detected in cervical squamous cell carcinoma

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

Chromosomal aberrations are a hallmark of human papillomavirus (HPV)-induced cervical carcinogenesis. The aim of this project was to identify structural chromosomal aberrations which may be characteristic for intraepithelial neoplasias (CIN) and cervical carcinomas (CxCa). Two independent HPV16 immortalized keratinocyte cell lines (HPKIA, HPKII) were used as a cell culture model system for cervical carcinogenesis. Different passages of HPKIA and HPKII were analyzed by multicolor spectral karyotyping. Several chromosomal translocations were identified in HPK cells and were validated by interphase fluorescence in situ hybridization (I-FISH). Three unbalanced whole chromosome arm translocations, der(10;14), der(7;21), and der(7;12), were cell line specific. The presence and frequency of these...

The genetics of dyskeratosis congenita

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome associated with characteristic mucocutaneous features and a variable series of other somatic abnormalities. The disease is heterogeneous at the genetic and clinical levels. Determination of the genetic basis of DC has established that the disease is caused by a number of genes, all of which encode products involved in telomere maintenance, either as part of telomerase or as part of the shelterin complex that caps and protects telomeres. There is overlap at the genetic and clinical levels with other, more common conditions, including aplastic anemia (AA), pulmonary fibrosis (PF), and liver cirrhosis. Although part of the spectrum of disorders known to be associated with DC, it has emerged that mutations in telomere mai...

Editorial Board

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Thu, 01 Dec 2011 05:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

A novel t(8;13)(q21;q22) translocation in a pediatric lipoma

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

Pediatric lipomas are rare and their etiology is unknown. As in adult lipomas, a segment of 12q13-q15 has been documented as a common chromosomal rearrangement region. Here, we report a pediatric lipoma case without rearrangement of 12q13-q15 but with an apparently balanced translocation involving chromosomes 8 and 13 [t(8;13)(q21;q22)] detected by routine cytogenetic analysis, and small deletions on 5q21.1 and 8q21.11 detected by array comparative genetic hybridization. The small deletion on 8q21.11 is possibly due to chromosomal instability at the breakpoint of the translocation. (Source: Cancer Genetics and Cytogenetics)

Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis, cytopenias, and a risk of transformation to acute myeloid leukemia (AML). However, only approximately 50% of primary MDS patients show clonal cytogenetic aberrations. To determine whether high-resolution microarray analysis would reveal new or additional aberrations, we analyzed 35 samples derived from patients with a diagnosis or suspicion of MDS and abnormal karyotypes. We used a whole-genome oligonucleotide microarray with targeted coverage of approximately 1900 genes associated with hematologic and other cancers. Clinically relevant copy number aberrations (CNAs) were identified by microarray-based comparative genomic hybridization (aCGH) in all samples (range 1...

FOXL2 mutation and large-scale genomic imbalances in adult granulosa cell tumors of the ovary

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

This study provides the first correlation of FOXL2 mutation status and genomic imbalances in AGCTs, and it further elucidates the mechanisms for mutant allele imbalance in cancer. (Source: Cancer Genetics and Cytogenetics)

FISH-based determination of HER2 status in circulating tumor cells isolated with the microfluidic CEE™ platform

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

Determination of HER2 status in breast cancer patients is considered standard practice for therapy selection. However, tumor biopsy in patients with recurrent and/or metastatic disease is not always feasible. Thus, circulating tumor cells (CTCs) are an alternative source of tumor cells for analysis of HER2. An antibody cocktail for recovery of variable, high- and low-, EpCAM-expressing tumor cells was developed based on FACS evaluation and then verified by CTC enumeration (based on CK and CD45 staining) with comparison to EpCAM-only and with CellSearch® (n=19). HER2 fluorescence in situ hybridization (FISH) on all (CK+ and CK−) captured cells was compared to HER2 status on the primary tumors (n=54) of patients with late stage metastatic/recurrent breast cancer. Capture of low EpCAM-expr...

FISH and chips: the recipe for improved prognostication and outcomes for children with medulloblastoma

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

Rapidly evolving genomic technologies have permitted progressively detailed studies of medulloblastoma biology in recent years. These data have increased our understanding of the molecular pathogenesis of medulloblastoma, identified prognostic markers, and suggested future avenues for targeted therapy. Although current randomized trials are still stratified based largely on clinical variables, the use of molecular markers is approaching routine use in the clinic. In particular, integrated genomics has uncovered that medulloblastoma comprises four distinct molecular and clinical variants: WNT, sonic hedgehog (SHH), group 3, and group 4. Children with WNT medulloblastoma have improved survival, whereas those with group 3 medulloblastoma have a dismal prognosis. Additionally, integrated genom...

Editorial Board

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Tue, 01 Nov 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

t(9;22)(q34;q11.2) is a recurrent constitutional non-Robertsonian translocation and a rare cytogenetic mimic of chronic myeloid leukemia

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

The diagnosis of hematologic malignancy can be greatly aided by the detection of a cytogenetic abnormality. However, care must be taken to ensure that constitutional chromosomal abnormalities are not misattributed to a putative population of malignant cells. Here we present an unusual case in which a constitutional balanced t(9;22)(q34;q11.2) cytogenetically mimicked the acquired, t(9;22)(q34;q11.2), that is characteristic of chronic myeloid leukemia. Of special note, fluorescence in situ hybridization (FISH) analysis for this constitutional translocation (9;22)(q34;q11.2) using standard probes for BCR and ABL1 resulted in an abnormal pattern that was potentially misinterpretable as a BCR-ABL1 fusion. This is the first reported FISH analysis of a constitutional t(9;22)(q34;q11.2), and over...

Translocation t(2;11) is characteristic of collagenous fibroma (desmoplastic fibroblastoma)

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

Collagenous fibroma (desmoplastic fibroblastoma) is a rare, benign soft-tissue tumor composed of spindled and stellate-shaped cells embedded in a dense collagenous stroma. Recently, a translocation between chromosomes 2 and 11 or a rearrangement involving the chromosome 11q12 breakpoint was reported to be recurrent and unique in collagenous fibroma. Herein, we describe a case of collagenous fibroma arising in the left thigh of a 57-year-old man. Magnetic resonance imaging revealed a 5.5 cm soft-tissue mass deep relative to the vastus medialis with low signal intensity on both T1- and T2-weighted sequences. A marginal excision of the tumor was performed, and histopathologic features were consistent with collagenous fibroma. Cytogenetic analysis exhibited a reciprocal translocation involving...

Double CEBPE-IGH rearrangement due to chromosome duplication and cryptic insertion in an adult with B-cell acute lymphoblastic leukemia

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

In an adult case of B-cell acute lymphoblastic leukemia (B-ALL) with a complex karyotype, both chromosomes 14 were involved in unbalanced rearrangements, specifically, der(14)t(13;14)(q21;q21) and dup(14)(q11q32). Fluorescence in situ hybridization (FISH) detected two CEBPE-IGH rearrangements at the dup(14). One was found at the duplication breakpoint and the other derived from insertion of CEBPE into an apparently normal IGH locus. Hypotheses to account for these unusual chromosomal rearrangements are discussed. This case provides the first evidence that chromosome duplication and cryptic insertion produce the CEBPE-IGH fusion and that more than one CEBPE-IGH recombination can occur in a leukemic cell. Our findings confirm that deregulated CEBPE plays a crucial role in the pathogenesis of...

A complex MLL rearrangement identified five years after initial MDS diagnosis results in out-of-frame fusions without progression to acute leukemia

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

Chromosomal rearrangements of the MLL gene are uncommon in myelodysplastic syndromes (MDSs), and few studies of their molecular structures and oncogenic mechanisms exist. Here, we present a case of de novo MDS with a normal karyotype at initial diagnosis and a mild clinical course. Five years after the initial diagnosis, investigators identified a complex rearrangement of the MLL gene without progression to acute leukemia. The 5′ part of the MLL gene is fused out of frame with the LOC100131626 gene, and the 3′ part of the MLL gene out of frame with the TCF12 gene. Rapid amplification of complementary DNA 3′ ends yielded two main fusion transcripts, which is in concordance with the two described isoforms of the LOC100131626 gene. For both isoform-fusion transcripts, the open reading f...

HMGA2 and MDM2 expression in lipomatous tumors with partial, low-level amplification of sequences from the long arm of chromosome 12

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

Ordinary lipomas are cytogenetically characterized primarily by simple balanced chromosome aberrations with stable morphologies, most of which affect chromosome segment, 12q13-15, where the HMGA2 gene plays a key pathogenetic role. Atypical lipomatous tumors (ALTs) display supernumerary ring or giant marker chromosomes with amplification of several genes including HMGA2 and MDM2. A study of HMGA2 expression in a variety of adipocytic tumors showed aberrant expression in lipomas with 12q13-15 aberrations and ring chromosomes as well as in ALTs and well-differentiated liposarcomas (WDLSs), and frequent differential expression of HMGA2 exons 1–2 versus that of exons 4–5. A minor subset of adipocytic tumors harbors unbalanced karyotypes with extra copies of 12q sequences in structures that...

High resolution genomic profiling and classical cytogenetics in a group of benign and atypical meningiomas

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

Meningiomas are classified as benign, atypical, or anaplastic. The majority are sporadic, solitary, and benign tumors with favorable prognoses. However, the prognosis for patients with anaplastic meningiomas remains less favorable. High resolution genomic profiling has the capacity to provide more detailed information. Therefore, we analyzed genomic aberrations of benign and atypical meningiomas using single nucleotide polymorphism (SNP) array, combined with G-banding by trypsin using Giemsa stain (GTG banding), spectral karyotyping, and locus-specific fluorescence in situ hybridization (FISH). We confirmed frequently detected chromosomal aberrations in meningiomas and identified novel genetic events. Applying SNP array, we identified constitutional de novo loss or gain within chromosome ...

Integrative genomic analysis identifies CCNB1 and CDC2 as candidate genes associated with meningioma recurrence

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

Meningiomas are a common type of primary central nervous system tumor. Patients with atypical meningioma are difficult to treat and their disease often recurs. The aim of this study was to examine the role of CCNB1 and CDC2 as factors in recurrent meningiomas. A total of 37 sporadic meningioma samples were collected after surgery. The messenger RNA (mRNA) levels of the biomarkers CCNB1, CDC2, and MKI67 were tested using quantitative reverse transcription–polymerase chain reaction. We performed statistical analyses using ANOVA and Spearman correlation analysis. We found a significant upregulation in CCNB1 (1.5-fold), CDC2 (1.4-fold), and MKI67 (1.8-fold) expression in recurrent tumors in comparison with primary tumors (P < 0.05). Additionally, we found significant upregulation of CCNB1 ...

Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

Genomic information is being used to develop robust prognostic and predictive biomarkers that will provide companion diagnostics for emerging molecular targeted therapies. The genetics and associated molecular pathways in ovarian cancer are increasingly being used for the development of novel targeted drugs with a much greater therapeutic specificity than standard chemotherapy. This review will provide an update on recent research on the therapeutic opportunities presented by mutational alterations to the epidermal growth factor receptor (EGFR) and phosphatidylinositide-3-kinase (PI3K/AKT/mTOR) pathways. In addition, the role of the deficient BRCA1/2-mediated homologous recombination (HR) (“BRCAness”) pathway is presented. Understanding the molecular biology of these pathways in the co...

Editorial Board

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Sat, 01 Oct 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Microgranular variant of acute promyelocytic leukemia with normal conventional cytogenetics, negative PML/RARA FISH and positive PML/RARA transcripts by RT-PCR

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

The rare finding of a cytogenetically normal, fluorescence in situ hybridization (FISH)–negative, but PML/RARA reverse transcription–polymerase chain reaction (RT-PCR)–positive acute promyelocytic leukemia (APL) was recently reviewed by Kim et al. in the December 2010 issue of Cancer Genetics and Cytogenetics . Of the 13 cases described in the report, 11 were classified as the common hypergranular variant of APL. Two cases were classified as the microgranular variant of APL, although one of these cases was initially misdiagnosed as acute myeloid leukemia (AML) with differentiation . Because microgranular APL may be confused morphologically with other subtypes of acute myeloid leukemia, verification of the classic t(15;17) by conventional cytogenetic methods or of PML/RARA rearrangem...

Genomic profiling in high hyperdiploid acute myeloid leukemia: a retrospective study of 19 cases

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

Among patients with acute myeloid leukemia (AML), the rare group of complex aberrant karyotypes characterized by high hyperdiploidy (HH) is a subset with poor prognosis. Because of their rarity, few conventional cytogenetic studies have specifically addressed these patients. To identify DNA copy number aberrations at the submicroscopic level, we applied array-based comparative genomic hybridization (aCGH) to samples from 19 AML patients with complex karyotypes characterized by HH (≥49 chromosomes). We found a total of 155 imbalances (average: 8.2 per patient), and a high proportion of these imbalances involved whole chromosomes (n = 75). The chromosomes most commonly gained were chromosomes 8 (58%), 21 (42%), and 19 (32%). We identified 80 segmental genomic aberrations, and losses (n = 4...

Two alternatively spliced 5′BCR/3′JAK2 fusion transcripts in a myeloproliferative neoplasm with a three-way t(9;18;22)(p23;p11.3;q11.2) translocation

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs) are known to harbor alterations of the tyrosine kinase JAK2 (9p24), resulting in the constitutive autoactivation of the encoded protein. Here, we report an unclassifiable MPN case, BCR/ABL1-negative, showing a three-way t(9;18;22)(p23;p11.3;q11.2) translocation, which generates a 5′BCR/3′JAK2 gene by fusing BCR at intron 1 to JAK2 at intron 14 on the derivative chromosome 22. The fusion gene produced two alternatively spliced 5′BCR/3′JAK2 transcripts, fusing in-frame BCR exon 1 to JAK2 exon 15 and exon 17. This is the first report of the simultaneous occurrence of two BCR/JAK2 fusion transcripts in the same sample and of the longer transcript isoform (BCR exon 1 fused to JAK2 exon 15). Notably, both BCR/JAK2 encoded fus...

Monosomal complex karyotype in pediatric mixed phenotype acute leukemia

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

In this study, we analyzed the patient’s peculiar chromosomal abnormalities, as evaluated by array comparative genomic hybridization in combination with multicolor fluorescence in situ hybridization and cytogenetic analyses. (Source: Cancer Genetics and Cytogenetics)

A novel five-way translocation, t(3;9;13;8;14)(q27;p13;q32;q24;q32), with concurrent MYC and BCL6 rearrangements in a primary bone marrow B-cell lymphoma

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

Chromosomal translocations involving MYC at 8q24 are found in Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (BCLU). Here, we describe a novel five-way translocation, t(3;9;13;8;14)(q27;p13;q32;q24;q32), involving MYC, BCL6, and the immunoglobulin heavy locus (IGH@) in a 73-year-old man with BCLU. The bone marrow was massively infiltrated with 95.6% abnormal medium- to large-sized lymphoid cells without vacuoles. Flow cytometric analyses indicated that the infiltrating cells were positive for CD10, CD19, CD20, CD25, HLA-DR, and κ chain. Immunohistochemistry revealed that they were also positive for BCL2 and CD10, and weakly positive for BCL6. The MIB1 index was approximately 99%. G-banding ...

Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non–small cell lung cancer and surrounding tissues

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

We used methylation-sensitive high resolution melting analysis to assess methylation of CpG islands within the promoters of the TIMP4, GATA4, SOX18, and EGFL7 genes in samples of non–small cell lung cancer and surrounding apparently normal tissue and noncancerous lung tissues. We found that the promoter methylation was heterogeneous in both tumor and surrounding normal tissue. This is in contrast to healthy lung tissue, where the promoters were normally either non- or hypomethylated, and the heterogeneity of methylation was low. An increased heterogeneity of methylation in the normal tissues surrounding the tumor may suggest an early start of epigenetic processes preceding genetic and morphologic changes and can be used as a biomarker of early cancerization events. This analysis is an ea...

miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

microRNAs (miRNAs) play an important role in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In the current study, we defined the target genes and biological functions of miR-27 with a luciferase reporter assay and Western blot analysis. We verified that miR-27 levels were increased in gastric cancer tissues. The overexpression of miR-27 promoted the metastasis of AGS cells, whereas its depletion decreased cell metastasis. Up-regulation of miR-27 increased the levels of the epithelial–mesenchymal transition (EMT)-associated genes ZEB1, ZEB2, Slug, and Vimentin, as well as decreased E-cadherin levels. We demonstrated that miR-27 promoted EMT by activating the Wnt pathway. Finally, the APC gene was identified as the direct...

Centrosomal dysregulation in human metastatic melanoma cell lines

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

Correct partitioning of the replicated genome during mitosis is orchestrated by centrosomes, and chromosomal instability is a commonly reported feature of human cancer. Melanomas are notorious for their genetic instability and rapid clonal evolution that may be manifested as aggressive growth and facile generation of therapy-resistant variants. We characterized the centrosomal status, ploidy, and gene status (TP53, CDKN2A/B, BRAF, and NRAS) of 15 human metastatic melanoma cell lines. Cells were labelled for pericentrin (a centrosomal marker), DNA and α-tubulin, and scored for centrosome morphology, supernumerary centrosomes, and mitotic symmetry. The incidence of supernumerary centrosomes correlated with that of gross centrosomal abnormalities (r = 0.90), mitotic asymmetry (r = 0.90), and...

Editorial Board

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Thu, 01 Sep 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Erratum: Genomic analyses of primary and metastatic serous epithelial ovarian cancer

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Ofir Israeli, Walter H. Gotlieb, Eitan Friedman, Jacob Korach, Eddy Friedman, Boleslaw Goldman, Assaf Zeltser, Gilad Ben-Baruch, Shlomit Rienstein, Ayala Aviram-Goldring. Genomic analyses of primary and metastatic serous epithelial ovarian cancer. Cancer Genet Cytogenet 2004;154:16–21. (Source: Cancer Genetics and Cytogenetics)

Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Traditionally non-small cell lung cancer (NSCLC) has been regarded as a single disease in terms of both diagnosis and of therapy; however, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) respond differently to both molecular targeted and newly developed chemotherapies. Therefore, identifying the molecular differences between these tumor types will impact diagnostic and therapeutic decisions. Here, we performed a large-scale multidimensional microarray analysis of 261 primary NSCLC tumors (169 AC and 92 SqCC), integrating DNA copy number, DNA methylation and gene expression profiles to identify subtype-specific alterations. Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered genes with correspo...

Array-CGH analysis of solid tumors with apparent normal karyotypes

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Some solid tumors with apparent normal karyotypes are not normal. These results are false negatives and detected normal result is due to overtake of the culture by normal cells. Discard fresh tissues from 10 cases of solid tumors with apparent normal karyotype (liposarcoma, renal cell carcinoma, lymphoma, breast cancer) were analyzed by array-CGH using Agilent 44K arrays. Four cases (40%) had abnormalities detected with array CGH, which was not previously detected after conventional tissue culture and cytogenetic analysis chromosome analysis. The pilot experiments indicate that incorporation of array-CGH in routine cancer cytogenetics may be beneficial in decreasing false negative results due to cell culture issues. (Source: Cancer Genetics and Cytogenetics)

Application of SNP array analysis to further characterize genomic abnormalities in pediatric oncology cases

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

SNP microarray analysis is valuable in the characterization of previously identified chromosomal abnormalities and is essential in the identification of novel genomic changes that previously have been unappreciated. Conventional chromosome analysis, fluorescence in situ hybridization (FISH) and SNP array analyses were performed on samples from ten oncology patients (five newly diagnosed ALL, one relapsed ALL, one T-myeloid leukemia, one MDS, one AML and one patient with HLH immunodeficiency). Of the six patients diagnosed with ALL, three had abnormalites identified by chromosome analysis, and all but one case had abnormal FISH results. In addition, all six ALL cases had additional genomic abnormalities identified by SNP microarray analysis. Three patients (AML, MDS, HLH immunodeficiency) (...

Detection of balanced translocations in hematologic disorders by array CGH

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Microarray-based comparative genomic hybridization (aCGH) is a powerful technique that can detect copy-number alterations (CNAs) throughout the genome, but the standard method cannot detect balanced translocations, which are important markers for hematologic disease. We have developed a microarray-based technology coupled with linear DNA amplification, termed translocation-CGH (tCGH), that can identify and characterize balanced translocations in addition to CNAs. Multiplexing translocation detection has facilitated the development of nine different disease-specific panels with an ability to detect as many as 128 different translocations in a single panel test. The ability of this technology to detect clinically relevant balanced translocations and to identify specific partner genes has bee...

Copy number, loss of heterozygosity and amplification detection in formalin-fixed paraffin-embedded melanocytic lesions using molecular inversion probes

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

A significant number of melanocytic lesions are called indeterminate for malignancy using standard diagnostic techniques. For these cases, a sensitive and robust molecular method that provides multiple data points predictive of tumorigenicity would be useful. Previous molecular studies have demonstrated characteristic copy number alterations in melanoma. We have used molecular inversion probe (MIP) technology (OncoScan™, Affymetrix) to identify and characterize genomic alterations in formalin-fixed, paraffin-embedded (FFPE) melanocytic lesions. Sixty-four melanocytic lesions (23 benign nevi, 11 melanocytic lesions of uncertain malignant potential (MLUMP), 27 primary melanoma, 3 metastatic melanoma) were identified for this study. Genomic DNA was isolated from tissue scrolls and processed...

GenArray: uncovering novel and recurrent chromosomal alterations with diagnostic and prognostic value in hematological malignancies

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Traditional cytogenetic techniques such as chromosome analysis and FISH have provided valuable genetic information for the evaluation of hematological malignancies. However, many genomic abnormalities remain undetected due to the limitations intrinsic to these techniques. Recently, the introduction of DNA array-based technologies has enabled the identification of previously undetected copy number changes with an increased resolution and sensitivity and a more precise determination of genomic break points and gene content. We have designed, validated and clinically applied a combined targeted-whole genome custom oligonucleotide microarray for the evaluation of hematological malignancies. The use of this technology not only allowed us to confirm genetic alterations identified by chromosome a...

A gene expression profile test for the differential diagnosis of ovarian versus endometrial cancers

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Carcinomas that are either metastatic or involve both the ovary and endometrium can present a diagnostic dilemma. For example, endometrial cancers metastatic to the ovary can often mimic ovarian primaries on gross and microscopic examination. We have developed a gene expression profile test (Pathwork Tissue of Origin Endometrial Test) that distinguishes ovarian and endometrial cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 316–gene classification model. The test was validated in a blinded study using a pre-specified algorithm and microarray data files for 75 metastatic, poorly differentiated or undifferentiated FFPE tumor specimens that had either a known ovarian or endometrial diagnosis. Measures of test performance include overall agreement with the available di...

Dealing with sample aneuploidy and mosaicsm using the ASCAT algorithm on different SNP array platforms

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Cancer samples pose a challenging problem for analysis using microarray technology. The basic array CGH (aCGH) approach can confidently detect changes in copy number when a sample is measured against a normal control. However, the necessary normalization pre-processing step will essentially wash away the information associated with hyperdiploid samples. This can be an issue especially with cancer samples. Additionally, mosaic samples, due to different mixture of cells in the sample, can also severely complicate the analysis and interoperation of samples with microarray technology. One of the recently proposed approaches to simultaneously deal with these issues is called the Allele Specific Copy Number Analysis of Tumors (ASCAT) algorithm (1). The approach takes advantage of the SNP informa...

Copy number variations and loss of heterozygosity identified in myelodysplastic syndrome

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid neoplasms with high risk of progression to acute myeloid leukemia (AML). The molecular pathogenic mechanisms that underlie the transformation of MDS to AML are largely unknown. About 50% of MDS patients show no cytogenetic abnormalities, making monitoring disease progress in these patients difficult. We hypothesize that some cryptic genomic copy number variations (CNVs) and regions with copy number neutral loss of heterozygosity (CN-LOH) may be or harbor genetic events responsible for the disease transformation. We studied 80 patients with newly diagnosed MDS to evaluate genomic alterations using a custom designed cancer specific CGH microarray that targets over 500 cancer genes and more than 100 cancer-associated genomic...

Chromosomal microarray as a clinical tool for 13q14 deletion subtyping in chronic lymphocytic leukemia

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease which has proven amenable to subtyping through genomic microarray analysis. Initially, 13q14 deletions as an isolated finding were associated with a favorable prognosis. However, recent evidence has revealed significant heterogeneity within the 13q14 deletion subtype, thus, there is a clear clinical need for more precise stratification of 13q14 deletions at the genomic level. The minimal deleted region (MDR) includes: DLEU2, DLEU7, MIR15A/MIR16-1 and part of DLEU1. Recent studies suggest that in addition to the MDR, the size of the deletion and the involvement of the nearby tumor suppressor gene RB1 serve as an independent prognostic biomarker for disease progression. Nine individuals in whom a 13q deletion had previou...

Genome-wide analysis of chromosomal abnormalities in acute lymphoblastic leukemia

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Conventional karyotyping, the traditional method of establishing chromosomal abnormalities in acute lymphoblastic leukemia (ALL), is considered to be the gold standard in cytogenetics. The introduction of interphase FISH with specific probes and polymerase chain reaction (PCR) methods has been shown to improve the ability to find smaller changes including cryptic balanced translocations. But these techniques possess several characteristics that hinder their usefulness in specialized circumstances. Given that chromosomal changes are used to group subcategories of ALL, evaluate prognoses, and detect residual disease, proper identification of relevant abnormalities is crucial for patient management. Genomic microarray offers a high resolution analysis of copy number changes (CNCs), and singl...

Correlation of FOXL2 mutation status with genomic imbalances in adult granulosa cell tumors of the ovary

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

A means to an end – Microarray platform comparison for profiling whole-genome amplified and unamplified cancer DNA

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Microarray platform choice is important for clinical laboratories. While the cancer microarray community recognizes the advantage of detecting copy-neutral loss of heterozygosity (cnLOH) by SNP-arrays and acknowledging the high signal-to-noise ratio for copy number aberration (CNA) by oligo-arrays, data remain scarce on array performance using low-quantity or -quality DNA, a frequent problem for cancer studies. We validated 70 specimens from 59 patients with hematological malignancies, of which 15 were analyzed on up to four different array platforms. We also analyzed disseminated tumor cells from 30 prostate cancer patients, each containing 2 to 20 cells, using whole-genome-amplified (WGA) DNA. Data analysis was performed with the manufacturers’ and Nexus software. For samples yielding ...

Paratesticular leiomyoma with a der(14)t(12;14)(q15;q24)

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

While uterine leiomyomas are among the most common and best cytogenetically characterized solid tumors, leiomyomas at other sites are rare. Only two karyotypically abnormal leiomyomas in males have been reported to date, both of them with unspecific chromosome aberrations. We recently analyzed by G-banding a paratesticular leiomyoma, a tumor type not cytogenetically examined before, and found the pseudodiploid karyotype 46,XY,der(5)t(5;14)(q31;q24),der(14)t(12;14)(q15;q24). The leiomyoma cells demonstrated strong immunohistochemical nuclear expression of the HMGA2 protein, supporting a role of HMGA2 as the target gene in 12q14∼15 rearrangements. In uterine leiomyomas, the t(12;14)(q15;q24) is the most frequent translocation leading to overexpression of HMGA2, therefore it seems that a co...

FOXP1 and PAX5 are rare but recurrent translocations partners in acute lymphoblastic leukemia

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Here, we report the case of a 57-year-old man, who was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). His diagnostic workup identified a translocation t(3;9)(p13;p13). This is the fifth case reported to date that involved the forkhead box P1 gene (FOXP1) and paired box gene 5 (PAX5). The PAX5-FOXP1 translocation is a nonrandom aberration, which is recurrent in both childhood and in adult B-ALL, and may contribute to leukemogenesis by blocking differentiation of hematopoietic cells into mature B-cells. (Source: Cancer Genetics and Cytogenetics)

Identification of chromosomal breakpoints of cancer-specific translocations by rolling circle amplification and long-distance inverse PCR

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

We describe the use of rolling circle amplification and long-distance inverse polymerase chain reaction (LD-PCR) to identify chromosomal breakpoints and fusion genes in cancer cells carrying acquired translocations. This approach produced enough template for 100 inverse PCR reaction from as little as 20 ng of patient DNA, consequently enabling the use of up to 500 times less patient DNA compared to standard inverse PCR. The method is based on identifying restriction sites in a putative breakpoint area in a cancer-specific translocation, followed by circularization and amplification of the restriction DNA products by using T4 DNA ligase and Phi29 enzyme, respectively. The amplified DNA thus obtained is used as a template in long-distance inverse PCR to amplify and detect the precise breakpo...

Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Cancer genomes frequently undergo genomic instability resulting in accumulation of chromosomal rearrangement. To date, one of the main challenges has been to confidently and accurately identify these rearrangements by using short-read massively parallel sequencing. We were able to improve cancer rearrangement detection by combining two distinct massively parallel sequencing strategies: fosmid-sized (36 kb on average) and standard 5 kb mate pair libraries. We applied this combined strategy to map rearrangements in two breast cancer cell lines, MCF7 and HCC1954. We detected and validated a total of 91 somatic rearrangements in MCF7 and 25 in HCC1954, including genomic alterations corresponding to previously reported transcript aberrations in these two cell lines. Each of the genomes contains...

Comparison of methodologies for KRAS mutation detection in metastatic colorectal cancer

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

This study was designed to compare and evaluate the efficacy of four different methodologies—high resolution melting, Sanger sequencing, DxS kit, and SNaPshot—for KRAS mutation detection in a clinical setting. In total, 372 samples from patients with metastatic colorectal cancer were analyzed by high resolution melting and SNaPshot, with 184 of those being further analyzed by Sanger sequencing and 188 with the DxS kit. Sensitivities were compared after consensus findings were determined by the presence of the same result in two of the three methodologies used in each case. The frequency of KRAS codon 12 and 13 mutations in our population was 43.5%, and a discordant finding was observed in 22 samples. Comparing to Sanger sequencing, significantly more consensus mutations were detected b...

A single-center cytogenetic study of 629 Chinese patients with de novo acute myeloid leukemia—evidence of major ethnic differences and a high prevalence of acute promyelocytic leukemia in Chinese patients

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

In this study, we contribute cytogenetic data from a large series of 629 Chinese patients with de novo AML that were karyotyped in a single laboratory. A higher prevalence of acute promyelocytic leukemia was observed when compared with non-Chinese series. The difference was most prominent in the younger age group. Abnormalities at chromosomal region 11q23 and inv(16) seemed uncommon. These ethnic differences may indicate underlying genetic susceptibility to AML development and/or environmental differences. More comprehensive data on AML in the elder population are needed to assess the role of cytogenetics in predicting prognosis and guiding treatment in this large subgroup of patients. (Source: Cancer Genetics and Cytogenetics)

Molecular characterization of an EWSR1–POU5F1 fusion associated with a t(6;22) in an undifferentiated soft tissue sarcoma

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

This report is novel in that to our knowledge, it is the first complete molecular characterization of an EWSR1–POU5F1 fusion in a soft tissue sarcoma. Evaluation of existing data on the known EWSR1–POU5F1 tumors suggests that the fusion gene functions in a wide variety of cell types and may modify the differentiation state of cells, resulting in susceptibility to tumorigenesis. (Source: Cancer Genetics and Cytogenetics)

Which individuals undergoing BRACAnalysis need BART testing?

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Deleterious mutations in BRCA1 and BRCA2 include those identified by sequencing technology as well as large genomic rearrangements (LGR). The main testing laboratory in the United States, Myriad Genetics Laboratory (MGL), has defined criteria for inclusion of LGR testing (i.e., BRACAnalysis Rearrangement Test, or BART™) when BRCA1 and BRCA2 testing is ordered. We were interested in determining how many of our patients with LGR mutations in BRCA1 and BRCA2 fulfilled these MGL criteria. A retrospective chart review was performed on all individuals who underwent genetic testing at our institution since August 2006. Individuals who underwent LGR testing were classified as either having or not having a LGR in BRCA1 or BRCA2. Each individual’s history was classified as meeting MGL defined LG...

Highlights from the second annual Cancer Cytogenomics Microarray Consortium (CCMC) meeting

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

Cancer Genetics is privileged to publish the abstracts from the second annual meeting of the Cancer Cytogenomics Microarray Consortium (CCMC) held August 8th and 9th, 2011 in Chicago, Illinois. (Source: Cancer Genetics and Cytogenetics)

Editorial Board

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Mon, 01 Aug 2011 04:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cytogenetic and molecular characteristics of 25 Chilean patients with a variant Ph translocation

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

We report the cytogenetic evaluation of 25 vPh cases, which represents 6.8% of the CML cases diagnosed at one institution in 20 years. The breakpoints of the partners of the vPh in our patients agree with those reported previously, except for a novel 18q23. We found a low incidence of deletions of the der(9) (10%) and der(22) (5%) in these patients, contrasting with several reports in the literature. This finding may reflect the extensive spectrum of aberrations in vPh, and the possibility that a considerable group of these aberrations may not affect the genetic stability of 5′ABL1 and 3′BCR. Epidemiologic differences may also exist and could explain our results. These differences would require further investigation. (Source: Cancer Genetics and Cytogenetics)

Absence of TCR loci chromosomal translocations in cutaneous T-cell lymphomas

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

Chromosomal aberrations involving T-cell receptor (TCR) gene loci have been described in several T-cell malignancies. In primary cutaneous T-cell lymphomas (CTCL), the frequency of these aberrations has not yet been well established. We analyzed TCR gene loci (TCRAD, TCRB, and TCRG) status in CTCLs by fluorescence in situ hybridization (FISH). Twenty-five patients with CTCLs were included in the study: 13 Sézary syndromes (SS), six tumoral stage mycosis fungoides (MFt), and six primary cutaneous anaplastic large cell lymphomas CD30+ (cALCL-CD30+). FISH was performed with three break-apart probes flanking TCRAD (14q11), TCRB (7q34), and TCRG (7p14) loci in each case. TCR gene chromosomal rearrangements were not detected in any of the analyzed cases. Gains of TCRB and TCRG genes were observ...

Tumor suppressor gene ZAC/PLAGL1: altered expression and loss of the nonimprinted allele in pheochromocytomas

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

In conclusion, our study suggests the involvement of the imprinted ZAC gene in the pathogenesis of PCC. (Source: Cancer Genetics and Cytogenetics)

Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

Clinical variables associated with ecotropic viral integration site 1 (EVI1) translocations were evaluated in 42 consecutive chronic myeloid leukemia (CML) patients in myeloid blast crisis (MBC). Translocations were confirmed with fluorescence in situ hybridization, and Western blot analysis demonstrated EVI1 expression. Translocations of EVI1 were present in 3 of 24 (12%) patients whose disease evolved MBC before tyrosine kinase inhibitor (TKI) exposure, and 7 of 18 (39%) patients who had received one or more TKIs. Univariate analysis showed that prior TKI therapy was the only clinical variable that was significantly associated with EVI1 translocation (P = 0.047). TKI-resistant BCR–ABL1 mutations were present in 71% of MBC patients with EVI1 translocations at the time of disease progres...

Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma cell lines

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

Phenobarbital (PB), a nongenotoxic carcinogen, activates the nuclear constitutive active/androstane receptor (CAR), resulting in the transcriptional induction or repression of various hepatic genes. We previously demonstrated that liver tumors developed after chronic PB treatment only when CAR is present. To understand the molecular mechanism of tumor promotion, cDNA microarray analysis was performed. We identified tubulin alpha 8 (TUBA8) as one of the candidate genes that may be involved in liver tumor promotion. Tuba8 mRNA was induced with PB treatment in mouse livers before tumor development as well as in tumor tissues. Because the functions of TUBA8 are unknown in liver, we investigated the effects of TUBA8 gene expression on cell growth, proliferation, and cell migration. Sense or ant...

Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

We examined PPP2R2A deletion status in 141 PCa samples using Affymetrix SNP arrays. It was found that PPP2R2A was commonly (67.1%) deleted in tumor samples, including a homozygous deletion in three tumors (2.1%). We performed a mutation screen for PPP2R2A in 96 probands of hereditary prostate cancer families. No high risk mutations were identified. In addition, we re-analyzed 10 SNPs of PPP2R2A in sporadic PCa cases and controls. No significant differences in the allele and genotype frequencies were observed among either PCa cases and controls or PCa aggressive and non-aggressive cases. Taken together, these results suggest that a somatic deletion rather than germline sequence variants of PPP2R2A may play a more important role in PCa susceptibility. (Source: Cancer Genetics and Cytogenetic...

Interphase fluorescence in situ hybridization analysis detects a much higher rate of thyroid tumors with clonal cytogenetic deviations of the main cytogenetic subgroups than conventional cytogenetics

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

In benign thyroid lesions, three main cytogenetic subgroups, characterized by trisomy 7 or structural aberrations involving either chromosomal region 19q13.4 or 2p21, can be distinguished by conventional cytogenetics (CC). As a rule, these aberrations seem to be mutually exclusive. Interphase fluorescence in situ hybridization (I-FISH) analysis on benign as well as malignant thyroid neoplasias has been performed in the past, but rarely in combination with CC. In the present paper, we have analyzed 161 benign thyroid lesions both with CC and I-FISH on touch preparations by using a multi-target, triple-color FISH assay as well as dual-color break-apart probes for detection of the main cytogenetic subgroups. Within the samples, I-FISH detected tumors belonging to either of the subgroups more ...

Promiscuous partnerships in Ewing's sarcoma

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

Ewing’s sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing’s sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing’s sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing’s sarcoma and have since been used as diagnostic markers ...

Editorial Board

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Thu, 30 Jun 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Jumping translocations in bone marrow cells of pediatric patients with hematologic malignancies: a rare cytogenetic phenomenon

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

Jumping translocations (JTs) are uncommon constitutional or acquired chromosomal aberrations. JTs are caused by the translocation of a section of one chromosome into two or more different recipient chromosomes. Several mechanisms, such as pericentromeric heterochromatin decondensation, shortened telomeres, illegitimate recombination, virus infection, and chromosome instability, are proposed to induce JTs. However, the pathogenesis of JTs remains elusive . (Source: Cancer Genetics and Cytogenetics)

Inversion and deletion of 16q22 defined by array CGH, FISH, and RT-PCR in a patient with AML

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

Acute myelomonocytic leukemia with eosinophilia is commonly associated with pericentric inversions of chromosome 16, involving the core binding factor beta gene (CBFB) on 16q22 and the myosin heavy chain gene (MYH11) on 16p13. The inv(16)(p13q22) results in a fusion gene comprising the 5′CBFB gene and the 3′MYH11 gene on the short arm of chromosome 16. The fusion gene interferes with the normal transcription of the CBFA/CBFB heterodimer and disrupts myeloid differentiation. The inv(16) is associated with a good prognosis. The inv(16) with deletion of the 3′CBFB region of the gene is a very rare occurrence. Although the number of cases is small, inv(16) with a deleted 3′CBFB seems to be associated with a poorer prognosis than that generally associated with inv(16). Our patient was a...

Identification of a complex 17q rearrangement in a metanephric stromal tumor

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

We describe conventional (“R-bands” karyotyping) and molecular [fluorescence in situ hybridization (FISH), multicolor FISH, oligo array-comparative genomic hybridization] cytogenetic examinations of a metanephric stromal tumor in a 3-year-old boy. Cytogenetic analysis revealed a complex homogeneous gain between bands 17q22 and 17q25.3, resulting in partial triplication of the segment between bands 17q22 and 17q24.3, and duplication of the segment between bands 17q24.3 and 17q25.3. Cytogenetic confirmatory studies in metanephric stromal tumors are currently needed to assess 17q22q25.3 gain as a recurring cytogenetic abnormality of metanephric stromal tumors. (Source: Cancer Genetics and Cytogenetics)

On the prevalence of the PAX8-PPARG fusion resulting from the chromosomal translocation t(2;3)(q13;p25) in adenomas of the thyroid

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

The chromosomal translocation t(2;3)(q13;p25) characterizes a subgroup of tumors originating from the thyroid follicular epithelium and was initially discovered in a few cases of adenomas. Later, a fusion of the genes PAX8 and PPARG resulting from this translocation was frequently observed in follicular carcinomas and considered as a marker of follicular thyroid cancer. According to subsequent studies, however, this rearrangement is not confined to carcinomas but also occurs in adenomas, with considerably varying frequencies. Only five cases of thyroid adenomas with this translocation detected by conventional cytogenetics have been documented. In contrast, studies using reverse-transcription polymerase chain reaction (RT-PCR) detected fusion transcripts resulting from that translocation in...

Characterization of a novel t(2;5;11) in a patient with concurrent AML and CLL: a case report and literature review

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

Acute myeloid leukemia (AML) that occurs concurrent with a diagnosis of chronic lymphocytic leukemia (CLL) is rare, but the number of cases recognized has recently dramatically increased as a result of the application of flow cytometry. This raises a series of questions regarding the clinical characterization of mixed leukemia, whether this diagnosis possesses unique cytogenetic abnormalities, and the possible association between AML and CLL cell clones. The current study attempts to answer these questions by evaluating an 80-year-old man with concurrent diagnoses of AML-M0 and CLL. Routine G-banded chromosome, array based comparative genomic hybridization, and fluorescence in situ hybridization analyses were used to characterize complex chromosomal rearrangements in the patient's bone mar...

Clonal cytogenetic abnormalities in the plasma cell variant of Castleman disease

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

We report a localized plasma cell variant of CD (PC-CD) with clonal abnormalities. A human immunodeficiency virus–negative 35-year-old man sought care for vague abdominal pain and was found to have an isolated 6-cm mesenteric mass. PC-CD was diagnosed by integrating clinical, laboratory, morphologic, and immunophenotypic studies. Flow cytometric, immunohistochemical, and molecular IGH@ gene rearrangement studies were all negative for a clonal B or plasma cell population. A cytogenetic in situ culture analysis revealed an abnormal karyotype: 46,XY,add(6)(p23),add(7)(p15),del(7)(p15),add(9)(q22)[4]/46,XY,inv(9)(p13q22)[2]/46,XY,−3,+r[2]/46,XY[3]. A cytogenetic suspension culture showed a normal karyotype. On the basis of the morphologic and immunophenotypic features, these genetic change...

RB1 gene mutations in Iranian patients with retinoblastoma: report of four novel mutations

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

Mutations in the RB1 gene lead to retinoblastoma, which is the most common intraocular tumor in children under the age of 6. In the present survey, the mutations of 18 unrelated Iranian retinoblastoma patients were characterized. Mutation analysis of the RB1 gene was performed in patients by sequencing all coding regions and by multiplex ligation probe-dependent amplification analysis. Clinical signs and symptoms of the retinoblastoma patients were similar to those of previously described patients with retinoblastoma. Eight known mutations and four novel mutations (c.832_833insT, c.1943delC, c.1206C>T, and c.2029delG) were determined. In silico analysis of the c.1206C>T variant showed that exon 12 contained an SC-35 consensus sequence, and this variation disrupted the splicing enhancer ele...

Combined characterization of a pituitary adenoma and a subcutaneous lipoma in a MEN1 patient with a whole gene deletion

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

We describe a young woman who fulfilled the clinical and biochemical criteria for MEN1 syndrome, but DNA sequencing did not indicate any MEN1 mutations. She developed a prolactin-secreting pituitary macroadenoma, primary hyperparathyroidism with parathyroid hyperplasia, pancreatic lesions, and two subcutaneous lipomas. Array comparative genomic hybridization (aCGH) analysis of peripheral blood DNA revealed a heterozygous germline deletion at 11q13.1 that spanned at least 22.23 kilobases and contained the entire MEN1 gene. Integrated aCGH and cytogenetic analyses of the adenoma and lipoma tissues revealed somatic inactivation of the wild-type MEN1 allele by different routes: the second hit of MEN1 recessive oncogenesis leading to adenoma implied a loss of heterozygosity, whereas a balanced ...

A study of adrenocortical tumors in children and adolescents by a comparative genomic hybridization technique

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

Adrenocortical tumors (ACT) are rare neoplasms of the adrenal glands accounting for 0.2% of all pediatric cancers. However, the incidence of ACT in South Brazilian children is 10 to 15 times greater than the worldwide incidence. Comparative genomic hybridization studies have revealed the presence of a high degree of chromosomal instability in ACT. We evaluated 16 ACT, 8 of them carcinomas and 8 adenomas. The presence of changes in DNA copy numbers was determined by comparative genomic hybridization, and the findings were validated by real-time polymerase chain reaction on the basis of IGF-II gene expression. The adenomas showed a mean of 19.7 imbalances per case, with the most frequent gain and loss being 4p15.1–p15.3 and 20p11.2–p13.2, respectively. The carcinomas presented with a me...

Clinical genomics of renal epithelial tumors

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

Kidney and upper urinary tract cancers account for approximately 54,000 cases every year in the United States, and represent about 3.7% of adult malignancies, with more than 13,000 annual deaths. Classification of renal tumors is typically based on histomorphologic characteristics but, on occasion, morphologic characteristics are not sufficient. Each of the most common histologic subtypes harbors specific recurrent genetic abnormalities, such as deletion of 3p in conventional clear cell carcinoma, trisomy 7 and 17 in papillary renal cell carcinoma, multiple monosomies in chromophobe renal cell carcinoma, and a nearly diploid genome in benign oncocytomas. Knowledge of this information can provide diagnostic support and prognostic refinement in renal epithelial tumors. Identification of the ...

Editorial Board

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Tue, 31 May 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Identification of genetic susceptibility to childhood cancer through analysis of genes in parallel

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

Sharon E. Plon, David A. Wheeler, Louise C. Strong, Gail E. Tomlinson, Michael Pirics, Qingchang Meng, Hannah C. Cheung, Phyllis R. Begin, Donna M. Muzny, Lora Lewis, Jaclyn A. Biegel, Richard A. Gibbs. Cancer Genet 2011;204:19–25. (Source: Cancer Genetics and Cytogenetics)

Glioblastoma specimens with TP53 mutations do not show EGFRvIII amplification

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

Watanabe et al. described TP53 mutation and epidermal growth factor receptor (EGFR) amplification as being mutually exclusive . In 2003, however, Okada et al. showed that peripheral or local EGFR amplification occurs in four out of six cases presenting with a TP53 mutation. They suggested that EGFR amplification occurs commonly in glioblastomas (GBMs) with TP53 mutations, although this amplification occurs in a very small proportion of cells (less than 1%). In 2008, Yoshimoto et al. described a highly sensitive technique for detecting the EGFRvIII variant by means of specific RT-PCR. EGFRvIII, characterized by the deletion of 267 amino acids in the extracellular domain, is the most common EGFR variant in GBMs. Moreover, this mutation leads to the constitutive activation of the receptor ...

Increased sperm aneuploidy in two male carriers of germline TP53 mutations

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

Li-Fraumeni syndrome is a rare autosomal dominant cancer predisposition syndrome characterized by a broad spectrum of tumors. The disorder is caused by germline mutations in the TP53 gene. We studied chromosomes in the sperm of two male carriers of TP53 mutations. We observed increased sperm aneuploidy, mainly concerning the gonosomes when compared to four normal male controls. This observation may correlate with the involvement of the p53 protein in spermatogenesis, with its role in aneuploidy in cancer, and with the occurrence of two cases of Turner syndrome in families with germline TP53 mutations reported in the literature. (Source: Cancer Genetics and Cytogenetics)

The effect of TP53 codon 72 and RNASEL codon 462 polymorphisms on the development of cervical cancer in Argentine women

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

Epidemiological evidence suggests that genetic factors, such as variants in cancer suppressor genes, may play an important role in the etiology of cervical carcinoma. TP53 is an outstanding cell cycle regulator, mutated in most human cancers, and RNASEL is thought to be involved in antiviral and apoptotic responses. To determine whether TP53 Arg72Pro and RNASEL Arg462Gln polymorphisms are associated with susceptibility to cervical cancer, a case-control study of 98 cancer patients and 123 healthy controls was conducted. Cervical samples were genotyped for both polymorphisms by pyrosequencing technology. The association between cervical cancer risk and the studied SNPs was evaluated by logistic regression, and potential gene–gene interactions were studied by Multifactor Dimensionality Red...

An insertion/deletion polymorphism in the 3′ untranslated region of type I collagen a2 (COL1A2) is associated with susceptibility for hepatocellular carcinoma in a Chinese population

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

Hepatocellular carcinoma (HCC) is one of the most common and severe diseases in the world. Besides the influence of environmental factors, such as viral infection, an increasing number of novel genetic components identified by genome-wide association studies have been associated with predisposition to HCC. Thus, studies focusing on functional variants in these findings are indispensable. In the present study, based on in-silico analysis, we carried out a case-control study in a Chinese population (207 cases and 245 controls) to investigate the association between HCC susceptibility with a 7 base pair (bp) insertion/deletion polymorphism (rs3917) in the 3′UTR of COL1A2. Our results showed that the ins/del + del/del genotype had an odds ratio of 1.76 (95% C.I.=1.03–3.01; P=0.028) for dev...

Molecular characterization of a t(2;7) translocation linking CDK6 to the IGK locus in CD5− monoclonal B-cell lymphocytosis

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

In this study, we sequenced a t(2;7) in a patient with persistent but non-progressing CD5− MBL. This revealed a breakpoint at 2p11.2 localized to the recombination signal sequence (RSS) of the immunoglobulin κ (IGK) variable gene IGKV3-15, and a breakpoint at 7q21.2 located 520 base pairs (bp) upstream of the transcription start site of cyclin-dependent kinase 6 (CDK6 ). The 7q breakpoint showed perfect sequence homology to the immunoglobulin RSS heptamer, and was located within 3 bp of a t(2;7) junction previously characterized in splenic marginal zone lymphoma (SMZL). These findings highlight a genetic link between CD5− MBL and SMZL, and implicate the dysregulation of CDK6 in the emergence of this preclinical disorder. (Source: Cancer Genetics and Cytogenetics)

Expression of HOXB genes is significantly different in acute myeloid leukemia with a partial tandem duplication of MLL vs. a MLL translocation: a cross-laboratory study

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

In this study, we first explored the differentially expressed genes between MLL-PTD and tMLL using gene expression profiling of our cohort (15 MLL-PTD and 10 tMLL) and one published data set. The top 250 probes were chosen from each set, resulting in 29 common probes (21 unique genes) to both sets. The selected genes include four HOXB genes, HOXB2, B3, B5, and B6. The expression values of these HOXB genes significantly differ between MLL-PTD and tMLL cases. Clustering and classification analyses were thoroughly conducted to support our gene selection results. Second, as MLL-PTD, FLT3-ITD, and NPM1 mutations are identified in AML with normal karyotypes, we briefly studied their impact on the HOXB genes. Another contribution of this study is to demonstrate that using public data from other ...

Correlation of polypoid colorectal adenocarcinoma with pre-existing adenomatous polyps and KRAS mutation

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

Cetuximab is an anti–epidermal growth factor receptor that helps effectively treat patients with advanced colorectal adenocarcinoma without KRAS activating mutations. KRAS mutations are associated with 16% to 50% of isolated villous adenomas and approximately 30% of colorectal cancer. Correlation between the gross and histological subset of colorectal adenocarcinoma with KRAS mutation is unknown. Archived surgical resection specimens of colorectal adenocarcinoma (n = 42) and villous adenoma (n = 9) were collected. The gross appearance and histopathological features of these lesions were thoroughly reviewed, including the presence of a pre-existing adenomatous polyp. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and then subjected to TaqMan real-time polymerase ...

Pediatric leukemia predisposition syndromes: clues to understanding leukemogenesis

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

The study of cancer predisposition syndromes leads to identification and understanding of mutations in genes coding for proteins and cellular pathways leading to cancer development, as well as normal cell growth and death regulators. Many patients with cancer predisposition syndromes experience excess toxicity with standard therapeutic regimens and are at lifelong risk for development of additional cancers and must be followed closely; early diagnosis is crucial for appropriate management of these patients. This review describes specific leukemia-predisposing conditions, including the clinical and historical findings that should trigger testing for these syndromes, and discusses recent insights into the management of these disorders. Disorders are organized by mechanism: (1) DNA damage rep...

Editorial Board

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Sat, 30 Apr 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Prostate cancer in Cowden syndrome: somatic loss and germline mutation of the PTEN gene

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

Germline mutations of PTEN, a tumor suppressor gene, cause a spectrum of autosomal-dominant hamartoma tumor syndrome overgrowth disorders, including Cowden syndrome (CS, MIM#158350) . Consensus diagnostic criteria for CS and guidelines for screening of cancer (breast, endometrium, thyroid, kidney, and skin) have been developed by the National Comprehensive Cancer Network (NCCN) . Somatic loss of PTEN has been described in sporadic counterpart tumors of CS as well as sporadic tumors not a component of CS: glioblastoma multiforme, melanoma, lung, pancreas, bladder, colon, and prostate. (Source: Cancer Genetics and Cytogenetics)

Establishment and characterization of a novel acute myeloid leukemia cell line, JIH-4, carrying a t(16;21)(p11.2;q22) and expressing the FUS-ERG fusion

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

We report a novel AML cell line, designated JIH-4, for which karyotypic analysis demonstrated a single abnormality, t(16;21)(p11.2;q22). The FUS-ERG fusion transcript was identified by reverse transcriptase polymerase chain reaction (RT-PCR). Neither Epstein-Barr virus nor mycoplasma was detected in JIH-4 cells. The morphology and immunoprofile of JIH-4 cells display typical features of myelogenous lineage, and short tandem-repeat PCR comparison with the donor patient’s bone marrow cells confirm the cell line’s authenticity. Tumor masses were found in 50% of inoculated mice 83 days after subcutaneous injection with JIH-4 cells. Our results confirm that JIH-4 cells are derived from the donor patient’s leukemia cells and support using the JIH-4 cell line as a valuable tool in the study...

Evaluating chromosomal mosaicism by array comparative genomic hybridization in hematological malignancies: the proposal of a formula

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

Array-based comparative genomic hybridization (aCGH) has proven indispensable to the study of unbalanced constitutional and acquired chromosomal anomalies, but its sensitivity for detecting mosaicism is still not well established. On the basis of the ADM2 algorithm used for microarray image analysis with one of the most widely used oligomer-based aCGH platforms [the whole genome 244K system by Agilent Technologies (Santa Clara, CA)] we suggest a formula to infer the percentage of cells bearing a chromosome imbalance in cases with constitutional or acquired mosaicism. Three examples of acquired mosaicism in which this formula was applied are reported together with parallel fluorescence in situ hybridization (FISH) to interphase nuclei with informative probes. Although some approximation aff...

Translocation t(7;19)(q22;q13)—a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma?

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

Pseudomyogenic hemangioendothelioma is a recently described morphologic entity among soft tissue tumors. It is more common in young individuals, shows a male predominance, is often multifocal and involves different tissue planes, and shows a high propensity for local recurrence. To our knowledge, no genetic characteristics of this tumor type have been presented before. Here, we describe the finding of a balanced t(7;19)(q22;q13) as the sole anomaly in three lesions from a 14-year-old girl. By means of fluorescence in situ hybridization, the breakpoints could be delineated, but reverse transcriptase–polymerase chain reaction for putative fusion genes did not reveal any fusion transcript. Interphase fluorescence in situ hybridization on sections from nine other pseudomyogenic hemangioendot...

Jumping translocation of chromosome 1q associated with good clinical outcome in a case of Burkitt leukemia

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

We report clinical, conventional and molecular cytogenetic findings of a 12-year-old boy who presented with BL. In addition to the primary aberration, t(8;14)(q24;q32), JT of 1q onto chromosomes 21 and der(14) as well as the formation of isochromosome 1q could be detected in his bone marrow sample. Despite the expected poor prognostic outcome of these aberrations, the patient has been experiencing an event free survival of 7.5 years at the time of the present report, reflecting the excellent clinical outcome of the disease. (Source: Cancer Genetics and Cytogenetics)

Chromosome banding analysis of cells from fine-needle aspiration biopsy samples from soft tissue and bone tumors: is it clinically meaningful?

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

Morphologic evaluation of samples from fine-needle aspiration (FNA) and core needle (CN) biopsies is an important part of the pretreatment diagnosis of bone and soft tissue tumors. Because most such tumors have characteristic, sometimes even specific, chromosomal rearrangements, ancillary genetic analyses could provide important diagnostic information. Whereas directed analyses, such as fluorescence in situ hybridization or reverse transcriptase–polymerase chain reaction, for specific genetic aberrations are well suited for the relatively small cell numbers obtained with FNA biopsies, the possibility to obtain tumor karyotypes after cell culturing has been less well studied. In the present study, karyotypes from 114 FNA biopsy samples were compared to those in corresponding surgical tumo...

Unknown partner for USP6 and unusual SS18 rearrangement detected by fluorescence in situ hybridization in a solid aneurysmal bone cyst

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

In conclusion, results obtained from commercially available FISH probes may occasionally yield misleading results. In this case, the SS18 rearrangement by FISH resulted from a complex rearrangement of 18q11.2 with a deletion of the SS18 gene. The translocation partner for USP6 remains unknown in this case. (Source: Cancer Genetics and Cytogenetics)

A cryptic deletion in 5q31.2 provides further evidence for a minimally deleted region in myelodysplastic syndromes

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

We present a case with a cryptic 1.3 Mb deletion in 5q31.2 identified by array comparative genomic hybridization that places the proximal boundary of the deletion proximal and close to the candidate EGR1 gene. The patient was diagnosed initially with a myelodysplastic syndrome, with a del(20)(q11.2q13.3) as the sole abnormality identified by karyotyping. The patient progressed to acute myeloid leukemia with no change to the G-banded karyotype. The 1.3 Mb deletion on the long arm of one chromosome 5 was confirmed to have been present both at presentation with myelodysplastic syndrome and at transformation. This is an interesting case because there are few array studies identifying cryptic 5q deletions, and the study of these small deletions helps to refine the common deleted region. This ca...

Cytogenetic findings in 14 benign cartilaginous neoplasms

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

We report a series of 14 chondromas from a single institution. Conventional cytogenetics was performed on short term cultures from all cases. Clonal chromosome aberrations were found in nine tumors. One soft tissue chondroma contained three clones with t(6;12)(q12;p11.2), t(3;7)(q13;p12), and der(2)t(2;18)(p11.2;q11.2). Three periosteal chondromas displayed random structural aberrations of chromosomes 2, 3, 6, 7, and 11 and loss of chromosome 13. Among the enchondromas, three tumors displayed chromosome losses, one contained a complex translocation involving chromosomes 12, 15, and 21 as well as an inv(2)(p21q31),t(12;15;21)(q13;q14;q22) and a separate enchondroma showed a translocation involving chromosomes 12 and 22. Our data suggest that considerable cytogenetic heterogeneity exists amo...

Philadelphia Chromosome Symposium: commemoration of the 50th anniversary of the discovery of the Ph chromosome

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

This report summarizes highlights of the Philadelphia Chromosome Symposium: Past, Present and Future, held September 28, 2010, to commemorate the 50th anniversary of the discovery of the Philadelphia chromosome. The symposium sessions included presentations by investigators who made seminal contributions concerning the discovery and molecular characterization of the Ph chromosome and others who developed a highly successful therapy based on the specific molecular alteration observed in chronic myeloid leukemia. Additional presentations highlighted future opportunities for the design of molecularly targeted therapies for various types of cancer. Also included here are reminiscences connected with the discovery of the Ph chromosome by David Hungerford and Peter Nowell, the discovery that the...

Editorial Board

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Thu, 31 Mar 2011 23:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Development of t(8;21) and RUNX1–RUNX1T1 in the Philadelphia-positive clone of a patient with chronic myelogenous leukemia: additional evidence for multiple steps involved in disease progression

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

A 65-year-old patient with a high hemoglobin and hematocrit was treated for 14 months with therapeutic phlebotomy when cytogenetics of bone marrow revealed 100% cells with the Ph chromosome and 45% of the Ph+ cells contained trisomy 8. Treatment with tyrosine kinase inhibitors did not reduce the BCR-ABL1 fusion positive clone. Instead, the Ph positive cells acquired further the t(8;21)/RUNX1-RUNX1T1, del(4q) and trisomy 15 chromosomal abnormalities which were resistant to further treatment. Literature review revealed eight other patients who either had t(9;22) and t(8;21) simultaneously or developed t(8;21) in the Ph positive clone. We conclude that there are rare patients with CML who either present in blast crisis with coexistence of t(9;22) and t(8;21) with or without +8, or progress t...

CD5-positive, cyclinD1-negative mantle cell lymphoma with a translocation involving the CCND2 gene and the IGL locus

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

We present a CD5-positive, CCND1-negative B-cell lymphoma with a novel translocation involving CCND2 and the immunoglobulin lambda (IGL) gene. A 64-year-old male underwent resection of a polypoid mass of the ileum. Histology showed atypical, medium-sized lymphoid cells positive for CD20, CD5, CD43, and CCND2 by immunohistochemistry, and negative for CCND1, CCND3, and p27. Fluorescence in situ hybridization was negative for CCND1 abnormalities, but demonstrated a CCND2/IGL fusion. Clinical workup revealed stage IV disease. Current diagnostic criteria are insufficient for subclassifying this case, highlighting the need for additional studies on CCND2-translocated B-cell lymphomas to guide therapy appropriately. (Source: Cancer Genetics and Cytogenetics)

Unbalanced translocations of 20q in AML and MDS often involve interstitial rather than terminal deletions of 20q

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

We report here that dicentric chromosomes involving chromosome 20 with loss of the 20q12 putative tumor suppressor gene are often the result of more complex rearrangements, with the 20q12 region being lost by an interstitial deletion independent of the site of translocation. We found interstitial deletions of 20q in two thirds of the two-way translocations tested. This points to a more complex mechanism of translocation involving at least three breakpoints and two separate events, and raises questions about the order of these events and the significance of these abnormalities. (Source: Cancer Genetics and Cytogenetics)

Identification of the TAF15–ZNF384 fusion gene in two new cases of acute lymphoblastic leukemia with a t(12;17)(p13;q12)

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

We report the clinical, cytogenetic, and molecular data of two patients diagnosed with acute lymphoblastic leukemia characterized by the rare translocation t(12;17)(p13;q12). This translocation has been reported in 25 cases and its putative molecular consequence, the formation of a TAF15–ZNF384 fusion gene, in only six cases. We used fluorescence in situ hybridization followed by long-range polymerase chain reaction to find the translocation breakpoints. A fusion between TAF15 and ZNF384 was identified and confirmed by nucleotide sequencing. Our results confirm that the t(12;17)(p13;q12) leading to a TAF15–ZNF384 fusion gene characterizes a specific subgroup of acute lymphoblastic leukemia and suggest that two different breakpoints in TAF15 may be involved. Whether the two variants of ...

Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

This study assesses whether deregulation of microRNA (miRNA) expression is a post-transcriptional mechanism leading to gene expression changes in osteosarcoma. miRNA expression profiling was performed for 723 human miRNAs in 7 osteosarcoma tumors, and 38 miRNAs differentially expressed ≥10-fold (28 under- and 10 overexpressed) were identified. In most cases, observed changes in miRNA expression were DNA copy number-correlated. However, various mechanisms of alteration, including positional and/or epigenetic modifications, may have contributed to the expression change of 23 closely linked miRNAs in cytoband 14q32. To develop a comprehensive molecular genetic map of osteosarcoma, the miRNA profiles were integrated with previously published array comparative genomic hybridization DNA imbala...

High resolution array comparative genomic hybridization identifies copy number alterations in diffuse large B-cell lymphoma that predict response to immuno-chemotherapy

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

Despite recent attempts at sub-categorization, including gene expression profiling into prognostically different groups of “germinal center B-cell type” and “activated B-cell type,” diffuse large B-cell lymphoma (DLBCL) remains a biologically heterogenous tumor with no clear prognostic biomarkers to guide therapy. Whole genome, high resolution array comparative genomic hybridization (aCGH) was performed on four cases of chemoresistant DLBCL and four cases of chemo-responsive DLBCL to identify genetic differences that may correlate with response to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Array CGH analysis identified seven DNA copy number alteration (CNA) regions exclusive to the chemoresistant group, consisting of amplifications at 1p...

Comparison of chromosomal aberrations in primary colorectal carcinomas to their pulmonary metastases

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

Pulmonary metastases (PM) are frequent in colorectal carcinoma (CRC). However, little is known about the chromosomal imbalances in CRC that accompany metastatic pulmonary disease. We investigated tumor specimens of CRC (n=30) and their corresponding PM by comparative genomic hybridization (CGH). There were no substantial differences in the degree of chromosomal instability between CRC and PM, neither in average number of copy alterations (ANCA; 6.6±0.8 and 7.7±0.9) nor in gains (2.6±0.5 and 2.6±0.4), losses (3.6±0.5 and 4.8±0.6), or amplifications (0.4±0.1 and 0.3±0.1). Basically, similar patterns of chromosomal imbalances could be identified in both CRC and corresponding PM, most frequently including chromosomal gains at 7, 8q, 13q, and 20q, as well as losses at 4, 8p, 18q, and 20...

Advances in the understanding of constitutional and somatic genomic alterations in neuroblastoma

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

Advances in the field of genomics have led to multiple recent discoveries in the understanding of genetic predisposition and molecular pathogenesis of the childhood cancer neuroblastoma. Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for 10% of childhood cancer related mortality. The genetic etiology of rare families with hereditary neuroblastoma is now largely understood, with the majority having activating mutations in the anaplastic lymphoma kinase (ALK) gene. Genome-wide association studies have identified multiple common, low penetrance genetic polymorphisms that are associated with a predisposition to sporadic neuroblastoma, and these associations are disease phenotype specific. While many of the discoveries related to variations in the host...

Editorial Board

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

Birgitte S. Preiss, Olav J. Bergman, Lone S. Friis, Anne G. Sørensen, Michael Frederiksen, Ole V. Gadeberg, Torben Mourits-Andersen, Birthe Oestergaard, Gitte B. Kerndrup, for the AML Study Group of Southern Denmark. Cancer Genet Cytogenet 2010;202:108-122. (Source: Cancer Genetics and Cytogenetics)

Secondary PSF/TFE3-associated renal cell carcinoma in a child treated for genitourinary rhabdomyosarcoma

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

We describe a child who developed a t(X;1)(p11.2;p34) associated RCC after previous treatment for genitourinary rhabdomyosarcoma in infancy. The presence of the PSF-TFE3 fusion has only been described in a very limited number of cases. Our report expands the spectrum of tumors in which RCC can arise in the pediatric age group after chemotherapy. (Source: Cancer Genetics and Cytogenetics)

Cytogenetic and molecular characterization of a hepatosplenic T-cell lymphoma: report of a novel chromosomal aberration

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

We describe the clinical, immunophenotypic, cytogenetic, fluorescence in situ hybridization, and molecular analyses for T cell receptor gene rearrangement in a 21-year-old man diagnosed with HSTCL. Immunophenotypic analysis revealed negativity for CD5 as well as double negativity for CD4/CD8 mature T-cell immunophenotype, which suggested the diagnosis of hepatosplenic T-cell lymphoma. Molecular analysis confirmed a TCR gene rearrangement, thereby verifying the common T-cell origin of the present HSTCL case. Furthermore, cytogenetic analysis revealed a novel chromosomal rearrangement, t(7;15)(p22;q21). Metaphase fluorescence in situ hybridization analysis confirmed the translocation of a chromosomal segment from 15q21 to 7p22. (Source: Cancer Genetics and Cytogenetics)

Paired distribution of molecular subtypes in bilateral breast carcinomas

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

The last decade has revealed fundamental new insight into the existence of intrinsic molecular subclasses of breast carcinomas. By using immunostaining on archival tissue, we classified tumor pairs from 50 patients with bilateral disease into molecular subgroups (luminal, triple-negative basal-like, and triple-negative unclassified). Synchronous tumors showed a slightly higher rate of concordant pairs than metachronous tumors, and luminal tumors were highly concordant regardless of being synchronous or metachronous (P = 0.001 and P = 0.002, respectively). Metachronous cases had a higher degree of discordance if the time interval was longer than 10 years; this was most pronounced for triple-negative tumors. The relationship found between subtypes of bilateral tumors provides additional evid...

Identification of chromosome aberrations in sporadic microsatellite stable and unstable colorectal cancers using array comparative genomic hybridization

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

In this study, we used array comparative genomic hybridization (aCGH) to identify genomic hotspot regions that harbor recurrent copy number changes. The study material comprised fresh samples from 40 MSS tumors and 20 MSI tumors obtained from 60 Danish CRC patients. We identified five small genomic regions ( (Source: Cancer Genetics and Cytogenetics)

Enhanced detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide in combination with pokeweed mitogen and phorbol myristate acetate

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

We report here use of a novel, stable CpG, GNKG168 along with pokeweed mitogen (PWM) and phorbol 12-myristate 13-acetate (PMA) for conventional cytogenetic assessment in CLL. We demonstrate that the combined use of GNKG168+PWM/PMA increased the sensitivity of detection of chromosomal abnormalities compared to PWM/PMA (n=207, odds ratio=2.2, P=0.0002) and GNKG168 (n=219, odds ratio=1.5, P=0.0452). Further, a significant increase in sensitivity to detect complexity ≥3 with GNKG168+PWM/PMA compared to GNKG168 alone (odds ratio 8.0, P=0.0022) or PWM/PMA alone (odds ratio 9.6, P=0.0007) was observed. The trend toward detection of higher complexity was significantly greater with GNKG168+PWM/PMA compared to GNKG168 alone (P=0.0412). The increased sensitivity was mainly attributed to the additio...

Genomic alterations in myeloid neoplasms with novel, apparently balanced translocations

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

In this report, we investigate two apparently balanced translocations, t(6;17)(q23.3;p13.3) and t(2;13)(p21;q14.11), in patients with myeloid neoplasms and uncover concomitant microdeletions associated with the breakpoints. Breakpoint mapping by fluorescence in situ hybridization (FISH) detected deletions at or adjacent to all breakpoints. Subsequently, array comparative genomic hybridization on the 244K Agilent platform refined the deletion boundaries, revealing a 1.7 Mb deletion directly adjacent to the 6q23.3 breakpoint, and a 562 kb deletion at 17p13.3 in the first case. The second case was found to harbor a 195 kb deletion at 2p21 and a 1.4 Mb deletion distal to the 13q breakpoint at 13q14.3. Additionally, a 133 kb deletion within the breakpoint region at 13q14.11 and a 265 kb deletio...

Cytogenomic aberrations associated with prostate cancer

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

Genetic changes associated with prostate cancer have finally begun to elucidate some of the mechanisms involved in the etiology of this complex and common disease. We highlight consistent and relatively frequent abnormalities seen by various methodologies. Specifically, the results of conventional and molecular cytogenetic studies, genome-wide association studies with single nucleotide polymorphisms, recurrent gene fusions, and epigenetic analyses are discussed. (Source: Cancer Genetics and Cytogenetics)

Editorial Board

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cover 1

Cancer Genetics and Cytogenetics — Tue, 01 Feb 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Translocation (Y;12) in lipoma

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

Lipomas are the most common benign mesenchymal neoplasm in adults, and have been extensively characterized at the cytogenetic level. Chromosomal aberrations have been observed in the majority of lipomas, two-thirds of which involve chromosomal region 12q14.3. To date, structural rearrangements have been reported affecting every chromosome except chromosome Y. Here we report a case of a lipoma that shows a novel apparently balanced translocation involving chromosomes Y and 12. Fluorescence in situ hybridization using a break-apart HMGA2 in-house probe set detected a single signal on the normal chromosome 12 but not on either the derivative chromosome Y or 12, indicating a cryptic loss of 12q14.3, where HMGA2 is mapped. Immunohistochemical studies, however, revealed overexpression of HMGA2 w...

Exon scanning by reverse transcriptase–polymerase chain reaction for detection of known and novel EML4–ALK fusion variants in non–small cell lung cancer

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

Chromosomal inversions within chromosome 2p, resulting in fusions between the echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) genes, are a recent focus of treatment options for non–small cell lung cancer. Thirteen EML4–ALK fusion variants have been identified, affecting eight EML4 exons. We have developed an exon scanning approach using multiplex reverse transcriptase–polymerase chain reaction (RT-PCR) to amplify known and potential variants involving the first 22 EML4 exons. A total of 55 formalin-fixed, paraffin-embedded lung cancer tumors were screened, of which 5 (9%) were positive for EML4–ALK fusions. Four positive cases harbored known fusion variants: variant 3a, 3b, or both in three cases and variant 1 in one case. The fifth posi...

Factors influencing a second myeloid malignancy in patients with Philadelphia-negative -7 or del(7q) clones during tyrosine kinase inhibitor therapy for chronic myeloid leukemia

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

The detection of Philadelphia-negative (Phneg) cells with non-random karyotypic abnormalities after tyrosine kinase inhibitor (TKI) therapy of chronic myeloid leukaemia (CML) can be associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). To our knowledge, however, there have been no studies on variables influencing the risk of MDS/AML in patients with specific Phneg karyotypes. We systematically examined studies reporting -7 or del(7q) within Phneg cells in TKI-treated CML patients, and abstracted clinical and cytogenetic data from individual reports into a standardized format for further analysis. Of 53 patients, 43 had Phneg -7 clones [as the sole abnormality (-7sole) in 29, or with other clones (-7dual) in 14], and del(7q) was present in 10. A total of 16/51 eval...

Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for patients with hematologic malignancies

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

Single nucleotide polymorphism–based oligonucleotide arrays have been used as a research tool to detect genomic copy number changes and allelic imbalance in a variety of hematologic malignancies and solid tumors. The high resolution, genome-wide coverage, minimal DNA requirements, and relatively short turnaround time are advantageous for use in a clinical setting. We validated the Illumina HumanHap550 BeadChip array for clinical use by analyzing 127 pediatric leukemia and lymphoma samples that had previously been characterized by means of standard cytogenetic analysis and fluorescence in situ hybridization. A higher resolution Illumina HumanHap610 BeadChip array was ultimately used for clinical testing. To date, 180 samples from children with a suspected or confirmed hematologic malignan...

Identification of genetic susceptibility to childhood cancer through analysis of genes in parallel

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

Clinical cancer genetic susceptibility analysis typically proceeds sequentially, beginning with the most likely causative gene. The process is time consuming and the yield is low, particularly for families with unusual patterns of cancer. We determined the results of in parallel mutation analysis of a large cancer-associated gene panel. We performed deletion analysis and sequenced the coding regions of 45 genes (8 oncogenes and 37 tumor suppressor or DNA repair genes) in 48 childhood cancer patients who also (i) were diagnosed with a second malignancy under age 30, (ii) have a sibling diagnosed with cancer under age 30, and/or (iii) have a major congenital anomaly or developmental delay. Deleterious mutations were identified in 6 of 48 (13%) families, 4 of which met the sibling criteria. M...

Distinct germ line polymorphisms underlie glioma morphologic heterogeneity

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

We report that specific germ line polymorphisms are associated with different glioma subtypes. CCDC26 (8q24) region polymorphisms are strongly associated with oligodendroglial tumor risk (rs4295627, odds ratio [OR] = 2.05, P = 8.3 × 10−11) but not glioblastoma risk. The opposite is true of RTEL (20q13) region polymorphisms, which are significantly associated with glioblastoma (rs2297440, OR = 0.56, P = 4.6 × 10−10) but not oligodendroglial tumor. The SNPs in or near CCDC26 (8q24) are associated with oligodendroglial tumors regardless of combined 1p and 19q deletion status; however, the association is greatest for those with combined deletion (rs4295627, OR = 2.77, P = 2.6 × 10−9). These observations generate hypotheses concerning the possible mechanisms by which specific SNPs (or ...

The prognostic significance of cytogenetics and molecular profiling in multiple myeloma

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

Multiple myeloma (MM) is a plasma cell malignancy characterized by very complex cytogenetic and molecular genetic aberrations. In newly diagnosed symptomatic patients, the modal chromosome number is usually either hyperdiploid with multiple trisomies or hypodiploid with one of several types of immunoglobulin heavy chain (Ig) translocations. The chromosome ploidy status and Ig rearrangements are two genetic criteria that are used to help stratify patients into prognostic groups based on the findings of conventional cytogenetics and fluorescence in situ hybridization (FISH). In general, the hypodiploid group with t(4;14)(p16;q32) or t(14;16)(q32;q23) is considered a high-risk group, while the hyperdiploid patients with t(11;14)(q13;q32) are considered a better prognostic group. As the diseas...

Editorial

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

Welcome to the first issue of Cancer Genetics, formerly Cancer Genetics and Cytogenetics. The inaugural issue of this journal was published in 1979, at a time when cancer cytogenetics was just emerging as a discipline, and investigators in pathology, oncology and genetics were only beginning to elucidate the genetic basis for hematologic malignancies and solid tumors. Dr. Avery Sandberg had the foresight to create a unique forum for publications in this field, and led this effort for 31 years. Dr. Sandberg recently concluded his tenure as editor-in-chief, and I am privileged and honored to assume this role with the January, 2011 issue of Cancer Genetics. (Source: Cancer Genetics and Cytogenetics)

Editorial Board

Cancer Genetics and Cytogenetics — Sat, 01 Jan 2011 00:00:00 +0100

(Source: Cancer Genetics and Cytogenetics)

Cancer Genetics and Cytogenetics via MedWorm.com

Table of Contents

Erratum: Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines

Sequential transient novel chromosomal translocations in a patient with chronic myelogenous leukemia in complete cytogenetic remission after therapy with imatinib mesylate

A possible 5′-NRIP1/UHRF1-3′ fusion gene detected by array CGH analysis in a Ph+ ALL patient

Single nucleotide polymorphism array-based karyotyping shows sequential genomic changes from monosomy to copy-neutral loss of heterozygosity of chromosome 7 and 20q deletion within a balanced translocation t(14;20) in AML

Similar cytogenetic findings in two synchronous secondary peripheral chondrosarcomas in a patient with multiple osteochondromas

Molecular cytogenetic characterization of epithelioid hemangioendothelioma

A t(1;9)(q10;q10) translocation with additional 6q23 and 9q22 rearrangements in a case of chondromyxoid fibroma

Clonal diversity analysis using SNP microarray: a new prognostic tool for chronic lymphocytic leukemia

Two novel unbalanced whole arm translocations are frequently detected in cervical squamous cell carcinoma

The genetics of dyskeratosis congenita

Editorial Board

Cover 1

Table of Contents

A novel t(8;13)(q21;q22) translocation in a pediatric lipoma

Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes

FOXL2 mutation and large-scale genomic imbalances in adult granulosa cell tumors of the ovary

FISH-based determination of HER2 status in circulating tumor cells isolated with the microfluidic CEE™ platform

FISH and chips: the recipe for improved prognostication and outcomes for children with medulloblastoma

Editorial Board

Cover 1

Table of Contents

t(9;22)(q34;q11.2) is a recurrent constitutional non-Robertsonian translocation and a rare cytogenetic mimic of chronic myeloid leukemia

Translocation t(2;11) is characteristic of collagenous fibroma (desmoplastic fibroblastoma)

Double CEBPE-IGH rearrangement due to chromosome duplication and cryptic insertion in an adult with B-cell acute lymphoblastic leukemia

A complex MLL rearrangement identified five years after initial MDS diagnosis results in out-of-frame fusions without progression to acute leukemia

HMGA2 and MDM2 expression in lipomatous tumors with partial, low-level amplification of sequences from the long arm of chromosome 12

High resolution genomic profiling and classical cytogenetics in a group of benign and atypical meningiomas

Integrative genomic analysis identifies CCNB1 and CDC2 as candidate genes associated with meningioma recurrence

Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer

Editorial Board

Cover 1

Table of Contents

Microgranular variant of acute promyelocytic leukemia with normal conventional cytogenetics, negative PML/RARA FISH and positive PML/RARA transcripts by RT-PCR

Genomic profiling in high hyperdiploid acute myeloid leukemia: a retrospective study of 19 cases

Two alternatively spliced 5′BCR/3′JAK2 fusion transcripts in a myeloproliferative neoplasm with a three-way t(9;18;22)(p23;p11.3;q11.2) translocation

Monosomal complex karyotype in pediatric mixed phenotype acute leukemia

A novel five-way translocation, t(3;9;13;8;14)(q27;p13;q32;q24;q32), with concurrent MYC and BCL6 rearrangements in a primary bone marrow B-cell lymphoma

Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non–small cell lung cancer and surrounding tissues

miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition

Centrosomal dysregulation in human metastatic melanoma cell lines

Editorial Board

Cover 1

Table of Contents

Erratum: Genomic analyses of primary and metastatic serous epithelial ovarian cancer

Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development

Array-CGH analysis of solid tumors with apparent normal karyotypes

Application of SNP array analysis to further characterize genomic abnormalities in pediatric oncology cases

Detection of balanced translocations in hematologic disorders by array CGH

Copy number, loss of heterozygosity and amplification detection in formalin-fixed paraffin-embedded melanocytic lesions using molecular inversion probes

GenArray: uncovering novel and recurrent chromosomal alterations with diagnostic and prognostic value in hematological malignancies

A gene expression profile test for the differential diagnosis of ovarian versus endometrial cancers

Dealing with sample aneuploidy and mosaicsm using the ASCAT algorithm on different SNP array platforms

Copy number variations and loss of heterozygosity identified in myelodysplastic syndrome

Chromosomal microarray as a clinical tool for 13q14 deletion subtyping in chronic lymphocytic leukemia

Genome-wide analysis of chromosomal abnormalities in acute lymphoblastic leukemia

Correlation of FOXL2 mutation status with genomic imbalances in adult granulosa cell tumors of the ovary

A means to an end – Microarray platform comparison for profiling whole-genome amplified and unamplified cancer DNA

Paratesticular leiomyoma with a der(14)t(12;14)(q15;q24)

FOXP1 and PAX5 are rare but recurrent translocations partners in acute lymphoblastic leukemia

Identification of chromosomal breakpoints of cancer-specific translocations by rolling circle amplification and long-distance inverse PCR

Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines

Comparison of methodologies for KRAS mutation detection in metastatic colorectal cancer

A single-center cytogenetic study of 629 Chinese patients with de novo acute myeloid leukemia—evidence of major ethnic differences and a high prevalence of acute promyelocytic leukemia in Chinese patients

Molecular characterization of an EWSR1–POU5F1 fusion associated with a t(6;22) in an undifferentiated soft tissue sarcoma

Which individuals undergoing BRACAnalysis need BART testing?

Highlights from the second annual Cancer Cytogenomics Microarray Consortium (CCMC) meeting

Editorial Board

Cover 1

Table of Contents

Cytogenetic and molecular characteristics of 25 Chilean patients with a variant Ph translocation

Absence of TCR loci chromosomal translocations in cutaneous T-cell lymphomas

Tumor suppressor gene ZAC/PLAGL1: altered expression and loss of the nonimprinted allele in pheochromocytomas

Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors

Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma cell lines

Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study

Interphase fluorescence in situ hybridization analysis detects a much higher rate of thyroid tumors with clonal cytogenetic deviations of the main cytogenetic subgroups than conventional cytogenetics

Promiscuous partnerships in Ewing's sarcoma

Editorial Board