Punctuated evolution of prostate cancer genomes Journal Article
| Authors: | Baca, S. C.; Prandi, D.; Lawrence, M. S.; Mosquera, J. M.; Romanel, A.; Drier, Y.; Park, K.; Kitabayashi, N.; MacDonald, T. Y.; Ghandi, M.; Van Allen, E.; Kryukov, G. V.; Sboner, A.; Theurillat, J. P.; Soong, T. D.; Nickerson, E.; Auclair, D.; Tewari, A.; Beltran, H.; Onofrio, R. C.; Boysen, G.; Guiducci, C.; Barbieri, C. E.; Cibulskis, K.; Sivachenko, A.; Carter, S. L.; Saksena, G.; Voet, D.; Ramos, A. H.; Winckler, W.; Cipicchio, M.; Ardlie, K.; Kantoff, P. W.; Berger, M. F.; Gabriel, S. B.; Golub, T. R.; Meyerson, M.; Lander, E. S.; Elemento, O.; Getz, G.; Demichelis, F.; Rubin, M. A.; Garraway, L. A. |
| Article Title: | Punctuated evolution of prostate cancer genomes |
| Abstract: | 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. © 2013 Elsevier Inc. |
| Keywords: | controlled study; gene sequence; somatic mutation; gene deletion; adenocarcinoma; cohort studies; genome-wide association study; carcinogenesis; prostate cancer; gleason score; prostatic neoplasms; cancer genetics; gene expression regulation, neoplastic; dna; gene rearrangement; molecular evolution; prostate adenocarcinoma; chromosome aberrations; tumor gene; genome, human; neuroendocrine tumors; clonal evolution |
| Journal Title: | Cell |
| Volume: | 153 |
| Issue: | 3 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2013-04-25 |
| Start Page: | 666 |
| End Page: | 677 |
| Language: | English |
| DOI: | 10.1016/j.cell.2013.03.021 |
| PUBMED: | 23622249 |
| PROVIDER: | scopus |
| PMCID: | PMC3690918 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):12 - "Export Date: 25 September 2013" - "CODEN: CELLB" - "Source: Scopus" |
