A comprehensive catalogue of somatic mutations from a human cancer genome.
All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
Pleasance
Erin D
ED
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Cheetham
R Keira
RK
Stephens
Philip J
PJ
McBride
David J
DJ
Humphray
Sean J
SJ
Greenman
Chris D
CD
Varela
Ignacio
I
Lin
Meng-Lay
ML
Ordóñez
Gonzalo R
GR
Bignell
Graham R
GR
Ye
Kai
K
Alipaz
Julie
J
Bauer
Markus J
MJ
Beare
David
D
Butler
Adam
A
Carter
Richard J
RJ
Chen
Lina
L
Cox
Anthony J
AJ
Edkins
Sarah
S
Kokko-Gonzales
Paula I
PI
Gormley
Niall A
NA
Grocock
Russell J
RJ
Haudenschild
Christian D
CD
Hims
Matthew M
MM
James
Terena
T
Jia
Mingming
M
Kingsbury
Zoya
Z
Leroy
Catherine
C
Marshall
John
J
Menzies
Andrew
A
Mudie
Laura J
LJ
Ning
Zemin
Z
Royce
Tom
T
Schulz-Trieglaff
Ole B
OB
Spiridou
Anastassia
A
Stebbings
Lucy A
LA
Szajkowski
Lukasz
L
Teague
Jon
J
Williamson
David
D
Chin
Lynda
L
Ross
Mark T
MT
Campbell
Peter J
PJ
Bentley
David R
DR
Futreal
P Andrew
PA
Stratton
Michael R
MR
D000328:Adult; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D057285:Precision Medicine; D017384:Sequence Deletion / Q000235:genetics; D014466:Ultraviolet Rays
D035683:MicroRNAs