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.
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sylvan C
authors.initials: SC
authors.lastname: Baca
authors.forename: Davide
authors.initials: D
authors.lastname: Prandi
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.forename: Alessandro
authors.initials: A
authors.lastname: Romanel
authors.forename: Yotam
authors.initials: Y
authors.lastname: Drier
authors.forename: Kyung
authors.initials: K
authors.lastname: Park
authors.forename: Naoki
authors.initials: N
authors.lastname: Kitabayashi
authors.forename: Theresa Y
authors.initials: TY
authors.lastname: MacDonald
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghandi
authors.forename: Eliezer
authors.initials: E
authors.lastname: Van Allen
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Kryukov
authors.forename: Andrea
authors.initials: A
authors.lastname: Sboner
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Theurillat
authors.forename: T David
authors.initials: TD
authors.lastname: Soong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nickerson
authors.forename: Daniel
authors.initials: D
authors.lastname: Auclair
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tewari
authors.forename: Himisha
authors.initials: H
authors.lastname: Beltran
authors.forename: Robert C
authors.initials: RC
authors.lastname: Onofrio
authors.forename: Gunther
authors.initials: G
authors.lastname: Boysen
authors.forename: Candace
authors.initials: C
authors.lastname: Guiducci
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Barbieri
authors.forename: Kristian
authors.initials: K
authors.lastname: Cibulskis
authors.forename: Andrey
authors.initials: A
authors.lastname: Sivachenko
authors.forename: Scott L
authors.initials: SL
authors.lastname: Carter
authors.forename: Gordon
authors.initials: G
authors.lastname: Saksena
authors.forename: Douglas
authors.initials: D
authors.lastname: Voet
authors.forename: Alex H
authors.initials: AH
authors.lastname: Ramos
authors.forename: Wendy
authors.initials: W
authors.lastname: Winckler
authors.forename: Michelle
authors.initials: M
authors.lastname: Cipicchio
authors.forename: Kristin
authors.initials: K
authors.lastname: Ardlie
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology