The landscape of somatic copy-number alteration across human cancers.
A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.
Beroukhim
Rameen
R
Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center.
Mermel
Craig H
CH
Porter
Dale
D
Wei
Guo
G
Raychaudhuri
Soumya
S
Donovan
Jerry
J
Barretina
Jordi
J
Boehm
Jesse S
JS
Dobson
Jennifer
J
Urashima
Mitsuyoshi
M
Mc Henry
Kevin T
KT
Pinchback
Reid M
RM
Ligon
Azra H
AH
Cho
Yoon-Jae
YJ
Haery
Leila
L
Greulich
Heidi
H
Reich
Michael
M
Winckler
Wendy
W
Lawrence
Michael S
MS
Weir
Barbara A
BA
Tanaka
Kumiko E
KE
Chiang
Derek Y
DY
Bass
Adam J
AJ
Loo
Alice
A
Hoffman
Carter
C
Prensner
John
J
Liefeld
Ted
T
Gao
Qing
Q
Yecies
Derek
D
Signoretti
Sabina
S
Maher
Elizabeth
E
Kaye
Frederic J
FJ
Sasaki
Hidefumi
H
Tepper
Joel E
JE
Fletcher
Jonathan A
JA
Tabernero
Josep
J
Baselga
José
J
Tsao
Ming-Sound
MS
Demichelis
Francesca
F
Rubin
Mark A
MA
Janne
Pasi A
PA
Daly
Mark J
MJ
Nucera
Carmelo
C
Levine
Ross L
RL
Ebert
Benjamin L
BL
Gabriel
Stacey
S
Rustgi
Anil K
AK
Antonescu
Cristina R
CR
Ladanyi
Marc
M
Letai
Anthony
A
Garraway
Levi A
LA
Loda
Massimo
M
Beer
David G
DG
True
Lawrence D
LD
Okamoto
Aikou
A
Pomeroy
Scott L
SL
Singer
Samuel
S
Golub
Todd R
TR
Lander
Eric S
ES
Getz
Gad
G
Sellers
William R
WR
Meyerson
Matthew
M
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D023281:Genomics; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D015398:Signal Transduction; D051020:bcl-X Protein / Q000235:genetics
C494811:BCL2L1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein