Patterns of somatic mutation in human cancer genomes.
Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.
Greenman
Christopher
C
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Stephens
Philip
P
Smith
Raffaella
R
Dalgliesh
Gillian L
GL
Hunter
Christopher
C
Bignell
Graham
G
Davies
Helen
H
Teague
Jon
J
Butler
Adam
A
Stevens
Claire
C
Edkins
Sarah
S
O'Meara
Sarah
S
Vastrik
Imre
I
Schmidt
Esther E
EE
Avis
Tim
T
Barthorpe
Syd
S
Bhamra
Gurpreet
G
Buck
Gemma
G
Choudhury
Bhudipa
B
Clements
Jody
J
Cole
Jennifer
J
Dicks
Ed
E
Forbes
Simon
S
Gray
Kris
K
Halliday
Kelly
K
Harrison
Rachel
R
Hills
Katy
K
Hinton
Jon
J
Jenkinson
Andy
A
Jones
David
D
Menzies
Andy
A
Mironenko
Tatiana
T
Perry
Janet
J
Raine
Keiran
K
Richardson
Dave
D
Shepherd
Rebecca
R
Small
Alexandra
A
Tofts
Calli
C
Varian
Jennifer
J
Webb
Tony
T
West
Sofie
S
Widaa
Sara
S
Yates
Andy
A
Cahill
Daniel P
DP
Louis
David N
DN
Goldstraw
Peter
P
Nicholson
Andrew G
AG
Brasseur
Francis
F
Looijenga
Leendert
L
Weber
Barbara L
BL
Chiew
Yoke-Eng
YE
DeFazio
Anna
A
Greaves
Mel F
MF
Green
Anthony R
AR
Campbell
Peter
P
Birney
Ewan
E
Easton
Douglas F
DF
Chenevix-Trench
Georgia
G
Tan
Min-Han
MH
Khoo
Sok Kean
SK
Teh
Bin Tean
BT
Yuen
Siu Tsan
ST
Leung
Suet Yi
SY
Wooster
Richard
R
Futreal
P Andrew
PA
Stratton
Michael R
MR
D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics
D009363:Neoplasm Proteins; D011494:Protein Kinases