Year: 2008
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using end sequencing profiling, which relies on paired-end sequencing of cloned tumor genomes. RESULTS: In the present study brain, breast, ovary, and prostate tumors, along with three breast cancer cell lines, were surveyed using end sequencing profiling, yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization confirmed translocations and complex tumor genome structures that include co-amplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms revealed candidate somatic mutations and an elevated rate of novel single nucleotide polymorphisms in an ovarian tumor. CONCLUSION: These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than was previously appreciated and that genomic fusions, including fusion transcripts and proteins, may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.
Source: Genome biology
Authors: Benjamin J Raphael, Stanislav Volik, Peng Yu, Chunxiao Wu, Guiqing Huang, Elena V Linardopoulou, Barbara J Trask, Frederic Waldman, Joseph Costello, Kenneth J Pienta, Gordon B Mills, Krystyna Bajsarowicz, Yasuko Kobayashi, Shivaranjani Sridharan, Pamela L Paris, Quanzhou Tao, Sarah J Aerni, Raymond P Brown, Ali Bashir, Joe W Gray, Jan-Fang Cheng, Pieter de Jong, Mikhail Nefedov, Thomas Ried, Hesed M Padilla-Nash, Colin C Collins
Institutions: Brown University, University of California, San Francisco, Chinese National Human Genome Center, Shandong University, Shandong Provincial Hospital, Fred Hutch Cancer Center, University of Michigan, Michigan Medicine, The University of Texas MD Anderson Cancer Center, Stanford University, University of California San Diego, Lawrence Berkeley National Laboratory, Joint Genome Institute, UCSF Benioff Children's Hospital, National Institutes of Health, National Cancer Institute, Center for Cancer Research
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,490
Funders: National Science Foundation, U.S. Department of Energy, Burroughs Wellcome Fund, Alfred P. Sloan Foundation, Prostate Cancer Foundation, Susan G. Komen, National Institutes of Health, Office of Science, University of California, San Francisco, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, Basic Energy Sciences, Medical Research and Materiel Command
Awards: G1171586233, G1286236842, G1286251239, G1477521472, G1863003419, COMPARATIVE GENOMIC ANALYSIS OF CARDIOVASCULAR GENE REGU, G216544311, G2242145091, G2913071099, G30714459, G3083819904, G3368471925, G3757255300, G382641700, G3884706689, G390041114, G419881185, G42916606, G4501827968, G498139845, G5004724115, SPORE in Breast Cancer, G6115279364, G645991424, G650090426, BIOLOGY OF OVARIAN CANCER, G6652958823, G6767173602, G7117962851, G75976900, G8076944143, G8243469821, The University of Texas M. D. Anderson Cancer Center SPORE in Ovarian Cancer, G8686699718, G9000009177, G9000100237, G9000329101, Cancer Center Support Grant, G969889393
OpenAlex ID: W2133105226