Transcriptome-guided characterization of genomic rearrangements in a breast cancer cell line

We have identified new genomic alterations in the breast cancer cell line HCC1954, using high-throughput transcriptome sequencing. With 120 Mb of cDNA sequences, we were able to identify genomic rearrangement events leading to fusions or truncations of genes including MRE11 and NSD1, genes already implicated in oncogenesis, and 7 rearrangements involving other additional genes. This approach demonstrates that high-throughput transcriptome sequencing is an effective strategy for the characterization of genomic rearrangements in cancers.

[1]  T. Dörk,et al.  Association of chromosomal locus 8q24 and risk of prostate cancer: a hospital-based study of German patients treated with brachytherapy. , 2009, Urologic oncology.

[2]  J. Sklar,et al.  A Neoplastic Gene Fusion Mimics Trans-Splicing of RNAs in Normal Human Cells , 2008, Science.

[3]  Peter Donnelly,et al.  A common sequence motif associated with recombination hot spots and genome instability in humans , 2008, Nature Genetics.

[4]  John L Hopper,et al.  Multiple loci with different cancer specificities within the 8q24 gene desert. , 2008, Journal of the National Cancer Institute.

[5]  G. Parmigiani,et al.  Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers , 2008, Proceedings of the National Academy of Sciences.

[6]  Neil A. Miller,et al.  Transcriptome sequencing of malignant pleural mesothelioma tumors , 2008, Proceedings of the National Academy of Sciences.

[7]  A. Chinnaiyan,et al.  Recurrent gene fusions in prostate cancer , 2008, Nature Reviews Cancer.

[8]  Norman Arnheim,et al.  Mammalian meiotic recombination hot spots. , 2007, Annual review of genetics.

[9]  A. Sparks,et al.  The Genomic Landscapes of Human Breast and Colorectal Cancers , 2007, Science.

[10]  J. Trachtenberg,et al.  Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer , 2007, British Journal of Cancer.

[11]  Chen-Yang Shen,et al.  Breast Cancer Risk Is Associated with the Genes Encoding the DNA Double-Strand Break Repair Mre11/Rad50/Nbs1 Complex , 2007, Cancer Epidemiology Biomarkers & Prevention.

[12]  K. Caldecott,et al.  DNA strand break repair and human genetic disease. , 2007, Annual review of genomics and human genetics.

[13]  Andrew Menzies,et al.  Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution. , 2007, Genome research.

[14]  G. Wang,et al.  NUP98–NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis , 2007, Nature Cell Biology.

[15]  Debashis Ghosh,et al.  Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer , 2007, Modern Pathology.

[16]  Yijun Ruan,et al.  Paired-end diTagging for transcriptome and genome analysis. , 2006, Current protocols in molecular biology.

[17]  G. Parmigiani,et al.  The Consensus Coding Sequences of Human Breast and Colorectal Cancers , 2006, Science.

[18]  Steven J. M. Jones,et al.  BMC Genomics BioMed Central Methodology article , 2006 .

[19]  C. Kai,et al.  CAGE: cap analysis of gene expression , 2006, Nature Methods.

[20]  L. Coussens,et al.  Tumor stroma and regulation of cancer development. , 2006, Annual review of pathology.

[21]  L. Coussens,et al.  Paradoxical roles of the immune system during cancer development , 2006, Nature Reviews Cancer.

[22]  J. Tchinda,et al.  Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. , 2006, Science.

[23]  D. Palli,et al.  MRE11 expression is impaired in gastric cancer with microsatellite instability. , 2004, Carcinogenesis.

[24]  J. Ptak,et al.  Three classes of genes mutated in colorectal cancers with chromosomal instability. , 2004, Cancer research.

[25]  C. Campbell,et al.  A Rad50-dependent pathway of DNA repair is deficient in Fanconi anemia fibroblasts. , 2004, Nucleic acids research.

[26]  R. Winqvist,et al.  Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility , 2003, Journal of medical genetics.

[27]  Alessandra Viel,et al.  Human MRE11 is inactivated in mismatch repair‐deficient cancers , 2002, EMBO reports.

[28]  Ji Huang,et al.  [Serial analysis of gene expression]. , 2002, Yi chuan = Hereditas.

[29]  J. Rowley,et al.  Chromosome translocations: dangerous liaisons revisited , 2001, Nature Reviews Cancer.

[30]  Emmanuel Dias-Neto,et al.  The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Chenchik,et al.  Reverse transcriptase template switching: a SMART approach for full-length cDNA library construction. , 2001, BioTechniques.

[32]  N. Kamada,et al.  Alterations of the double-strand break repair gene MRE11 in cancer. , 2001, Cancer research.

[33]  Rithy K. Roth,et al.  Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays , 2000, Nature Biotechnology.

[34]  R. Strausberg,et al.  The cancer genome anatomy project: building an annotated gene index. , 2000, Trends in genetics : TIG.

[35]  N. Samani,et al.  Exon repetition in mRNA. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[36]  A. Kerlavage,et al.  Complementary DNA sequencing: expressed sequence tags and human genome project , 1991, Science.

[37]  J. Rowley.  A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa Staining , 1973, Nature.