Punctuated Evolution of Prostate Cancer Genomes

详细信息    查看全文

• 作者：Sylvan C. Baca¹ ; ² ; ³ ; Davide Prandi⁶ ; Michael S. Lawrence² ; Juan Miguel Mosquera⁸ ; Alessandro Romanel⁶ ; Yotam Drier² ; ⁷ ; Kyung Park⁸ ; Naoki Kitabayashi⁸ ; Theresa Y. MacDonald⁸ ; Mahmoud Ghandi² ; Eliezer Van Allen² ; ³ ; Gregory V. Kryukov¹ ; ² ; ¹³ ; Andrea Sboner⁸ ; ⁹ ; Jean-Philippe Theurillat² ; T. David Soong⁹ ; Elizabeth Nickerson² ; Daniel Auclair² ; Ashutosh Tewari¹⁰ ; ¹¹ ; Himisha Beltran¹² ; Robert C. Onofrio² ; Gunther Boysen⁸ ; Candace Guiducci² ; Christopher E. Barbieri⁸ ; ¹¹ ; Kristian Cibulskis² ; Andrey Sivachenko² ; Scott L. Carter² ; Gordon Saksena² ; Douglas Voet² ; Alex H. Ramos¹ ; ² ; Wendy Winckler² ; Michelle Cipicchio² ; Kristin Ardlie² ; Philip W. Kantoff¹ ; ³ ; Michael F. Berger¹⁴ ; Stacey B. Gabriel² ; Todd R. Golub² ; ⁴ ; ⁵ ; ¹⁵ ; Matthew Meyerson¹ ; ² ; ³ ; ⁴ ; Eric S. Lander¹ ; ² ; ¹⁶ ; ¹⁷ ; Olivier Elemento⁹ ; Gad Getz² ; Francesca Demichelis⁶ ; ⁹ ; ¹⁸ ; ^{demichelis@science.unitn.it} ; Mark A. Rubin⁸ ; ¹¹ ; ¹⁸ ; Levi A. Garraway¹ ; ² ; ³ ; ⁴ ; ¹⁸ ; ^{levi_garraway@dfci.harvard.edu}
• 刊名：Cell
• 出版年：2013
• 出版时间：25 April, 2013
• 年：2013
• 卷：153
• 期：3
• 页码：666-677
• 全文大小：2254 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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.