期刊
CELL
卷 153, 期 3, 页码 666-677出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.03.021
关键词
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资金
- US National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program [U54 HG003067]
- Kohlberg Foundation
- Starr Cancer Consortium
- Prostate Cancer Foundation
- US Department of Defense Synergy Awards [PC101020]
- Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (US National Institutes of Health [NIH]) [P50 CA090381]
- US National Cancer Institute, Early Detection Research Network [U01CA111275]
- NCI EDRN
- US National Cancer Institute [R01 CA125612]
- Fondazione Trentina per la Ricerca sui Tumori
- Swiss Science Foundation [PASMP3_134379/1]
- National Institute of General Medical Sciences [T32GM007753]
- US NIH Director's New Innovator Award [DP2OD002750]
- Novartis
- [PC094516]
The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis.
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