Punctuated Evolution of Prostate Cancer Genomes

被引：963

作者：

Baca, Sylvan C. ^{[1
,2
,3
]}

Prandi, Davide ^{[6
]}

Lawrence, Michael S. ^{[2
]}

Mosquera, Juan Miguel ^{[8
]}

Romanel, Alessandro ^{[6
]}

Drier, Yotam ^{[2
,7
]}

Park, Kyung ^{[8
]}

Kitabayashi, Naoki ^{[8
]}

MacDonald, Theresa Y. ^{[8
]}

Ghandi, Mahmoud ^{[2
]}

Van Allen, Eliezer ^{[2
,3
]}

Kryukov, Gregory V. ^{[1
,2
,14
]}

Sboner, Andrea ^{[8
,9
]}

Theurillat, Jean-Philippe ^{[2
]}

Soong, T. David ^{[9
]}

Nickerson, Elizabeth ^{[2
]}

Auclair, Daniel ^{[2
]}

Tewari, Ashutosh ^{[10
,11
,12
]}

Beltran, Himisha ^{[13
]}

Onofrio, Robert C. ^{[2
]}

Boysen, Gunther ^{[8
]}

Guiducci, Candace ^{[2
]}

Barbieri, Christopher E. ^{[8
,12
]}

Cibulskis, Kristian ^{[2
]}

Sivachenko, Andrey ^{[2
]}

Carter, Scott L. ^{[2
]}

Saksena, Gordon ^{[2
]}

Voet, Douglas ^{[2
]}

Ramos, Alex H. ^{[1
,2
]}

Winckler, Wendy ^{[2
]}

Cipicchio, Michelle ^{[2
]}

Ardlie, Kristin ^{[2
]}

Kantoff, Philip W. ^{[1
,3
]}

Berger, Michael F. ^{[15
]}

Gabriel, Stacey B. ^{[2
]}

Golub, Todd R. ^{[2
,4
,5
,16
]}

Meyerson, Matthew ^{[1
,2
,3
,4
]}

Lander, Eric S. ^{[1
,2
,17
,18
]}

Elemento, Olivier ^{[9
]}

Getz, Gad ^{[2
]}

Demichelis, Francesca ^{[6
,9
]}

Rubin, Mark A. ^{[8
,12
]}

Garraway, Levi A. ^{[1
,2
,3
,4
]}

机构：

[1] Harvard Univ, Sch Med, Boston, MA 02115 USA

[2] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[4] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA

[5] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[6] Univ Trento, Ctr Integrat Biol, I-38123 Povo, Trento, Italy

[7] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel

[8] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA

[9] Weill Cornell Med Coll, Dept Physiol & Biophys, Inst Computat Biomed, New York, NY 10065 USA

[10] Weill Cornell Med Coll, Lefrak Ctr Robot Surg, New York, NY 10065 USA

[11] Weill Cornell Med Coll, Ctr Prostate Canc Res & Clin Care, New York, NY 10065 USA

[12] Weill Cornell Med Coll, Brady Fdn Dept Urol, New York, NY 10065 USA

[13] Weill Cornell Med Coll, Div Hematol & Med Oncol, Dept Med, New York, NY 10065 USA

[14] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[15] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[16] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[17] MIT, Dept Biol, Cambridge, MA 02139 USA

[18] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

来源：

CELL | 2013年 / 153卷 / 03期

基金：

美国国家卫生研究院;

关键词：

TMPRSS2-ERG FUSION; REARRANGEMENTS; CHD1; MUTATIONS; EVENT;

D O I：

10.1016/j.cell.2013.03.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：666 / 677

页数：12

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