Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, et al. Punctuated evolution of prostate cancer genomes. Cell. 2013;153:666–77.
NOTES
Baca, Sylvan CPrandi, DavideLawrence, Michael SMosquera, Juan MiguelRomanel, AlessandroDrier, YotamPark, KyungKitabayashi, NaokiMacDonald, Theresa YGhandi, MahmoudVan Allen, EliezerKryukov, Gregory VSboner, AndreaTheurillat, Jean-PhilippeSoong, T DavidNickerson, ElizabethAuclair, DanielTewari, AshutoshBeltran, HimishaOnofrio, Robert CBoysen, GuntherGuiducci, CandaceBarbieri, Christopher ECibulskis, KristianSivachenko, AndreyCarter, Scott LSaksena, GordonVoet, DouglasRamos, Alex HWinckler, WendyCipicchio, MichelleArdlie, KristinKantoff, Philip WBerger, Michael FGabriel, Stacey BGolub, Todd RMeyerson, MatthewLander, Eric SElemento, OlivierGetz, GadDemichelis, FrancescaRubin, Mark AGarraway, Levi AengP50 CA090381/CA/NCI NIH HHS/U54 HG003067/HG/NHGRI NIH HHS/T32 GM007753/GM/NIGMS NIH HHS/U01 CA162148/CA/NCI NIH HHS/R01 CA125612/CA/NCI NIH HHS/DP2OD002750/OD/NIH HHS/DP2 OD002750/OD/NIH HHS/R33 CA155554/CA/NCI NIH HHS/U01CA111275/CA/NCI NIH HHS/T32GM007753/GM/NIGMS NIH HHS/U01 CA111275/CA/NCI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Cell. 2013 Apr 25;153(3):666-77. doi: 10.1016/j.cell.2013.03.021.
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.
Last updated on 02/17/2021