Punctuated evolution of prostate cancer genomes

Sylvan C. Baca, Davide Prandi, Michael S. Lawrence, Juan Miguel Mosquera, Alessandro Romanel, Yotam Drier, Kyung Park, Naoki Kitabayashi, Theresa Y. MacDonald, Mahmoud Ghandi, Eliezer Van Allen, Gregory V. Kryukov, Andrea Sboner, Jean Philippe Theurillat, T. David Soong, Elizabeth Nickerson, Daniel Auclair, Ashutosh Tewari, Himisha Beltran, Robert C. OnofrioGunther Boysen, Candace Guiducci, Christopher E. Barbieri, Kristian Cibulskis, Andrey Sivachenko, Scott L. Carter, Gordon Saksena, Douglas Voet, Alex H. Ramos, Wendy Winckler, Michelle Cipicchio, Kristin Ardlie, Philip W. Kantoff, Michael F. Berger, Stacey B. Gabriel, Todd R. Golub, Matthew Meyerson, Eric S. Lander, Olivier Elemento, Gad Getz, Francesca Demichelis, Mark A. Rubin, Levi A. Garraway

Research output: Contribution to journalArticlepeer-review

964 Scopus citations


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.

Original languageEnglish
Pages (from-to)666-677
Number of pages12
Issue number3
StatePublished - 25 Apr 2013
Externally publishedYes


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