Year: 2008
Type: article
Abstract: The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP 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 (FISH) confirmed translocations and complex tumor genome structures that include coamplification 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 (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.
Authors: Collins, Colin, Raphael, Benjamin J., Volik, Stanislav, Yu, Peng, Wu, Chunxiao, Huang, Guiqing, Linardopoulou, Elena V., Trask, Barbara J., Waldman, Frederic, Costello, Joseph, Pienta, Kenneth J., Mills, Gordon B., Bajsarowicz, Krystyna, Kobayashi, Yasuko, Sridharan, Shivaranjani, Paris, Pamela, Tao, Quanzhou, Aerni, Sarah J., Brown, Raymond P., Bashir, Ali, Gray, Joe W., Cheng, Jan-Fang, de Jong, Pieter, Nefedov, Mikhail, Ried, Thomas, Padilla-Nash, Hesed M., Collins, Colin C.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Energy, Alfred P. Sloan Foundation, Prostate Cancer Foundation, 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, Basic Energy Sciences, Medical Research and Materiel Command
Awards: G1171586233, G1286236842, G1286251239, G1863003419, G216544311, G2242145091, G30714459, G3083819904, G382641700, G3884706689, G390041114, G419881185, G4501827968, G498139845, G5004724115, SPORE in Prostate Cancer, G650090426, G6767173602, G75976900, G9000329101, Model-based predictions of responses RTK Pathway therapies, G969889393
OpenAlex ID: W4298869780