title: A comprehensive catalogue of somatic mutations from a human cancer genome.
abstract: 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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
authors.forename: Erin D
authors.initials: ED
authors.lastname: Pleasance
authors.forename: R Keira
authors.initials: RK
authors.lastname: Cheetham
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.forename: David J
authors.initials: DJ
authors.lastname: McBride
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Humphray
authors.forename: Chris D
authors.initials: CD
authors.lastname: Greenman
authors.forename: Ignacio
authors.initials: I
authors.lastname: Varela
authors.forename: Meng-Lay
authors.initials: ML
authors.lastname: Lin
authors.forename: Gonzalo R
authors.initials: GR
authors.lastname: Ordóñez
authors.forename: Graham R
authors.initials: GR
authors.lastname: Bignell
authors.forename: Kai
authors.initials: K
authors.lastname: Ye
authors.forename: Julie
authors.initials: J
authors.lastname: Alipaz
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Bauer
authors.forename: David
authors.initials: D
authors.lastname: Beare
authors.forename: Adam
authors.initials: A
authors.lastname: Butler
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Carter
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cox
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Paula I
authors.initials: PI
authors.lastname: Kokko-Gonzales
authors.forename: Niall A
authors.initials: NA
authors.lastname: Gormley
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Grocock
authors.forename: Christian D
authors.initials: CD
authors.lastname: Haudenschild
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hims
authors.forename: Terena
authors.initials: T
authors.lastname: James
authors.forename: Mingming
authors.initials: M
authors.lastname: Jia
authors.forename: Zoya
authors.initials: Z
authors.lastname: Kingsbury
authors.forename: Catherine
authors.initials: C
authors.lastname: Leroy
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Andrew
authors.initials: A
authors.lastname: Menzies
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Mudie
authors.forename: Zemin
authors.initials: Z
authors.lastname: Ning
authors.forename: Tom
authors.initials: T
authors.lastname: Royce
authors.forename: Ole B
authors.initials: OB
authors.lastname: Schulz-Trieglaff
authors.forename: Anastassia
authors.initials: A
authors.lastname: Spiridou
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Stebbings
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szajkowski
authors.forename: Jon
authors.initials: J
authors.lastname: Teague
authors.forename: David
authors.initials: D
authors.lastname: Williamson
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ross
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: David R
authors.initials: DR
authors.lastname: Bentley
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
mesh_terms: 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
chemical_list: D035683:MicroRNAs