title: Prevalence of somatic alterations in the colorectal cancer cell genome.
abstract: Although a small fraction of human cancers have increased rates of somatic mutation because of known deficiencies in DNA repair, little is known about the prevalence of somatic alterations in the vast majority of human cancers. To systematically assess nonsynonymous somatic alterations in colorectal neoplasia, we used DNA sequencing to analyze approximately 3.2 Mb of coding tumor DNA comprising 1,811 exons from 470 genes. In total, we identified only three distinct somatic mutations, comprising two missense changes and one 14-bp deletion, each in a different gene. The accumulation of approximately one nonsynonymous somatic change per Mb of tumor DNA is consistent with a rate of mutation in tumor cells that is similar to that of normal cells. These data suggest that most sporadic colorectal cancers do not display a mutator phenotype at the nucleotide level. They also have significant implications for the interpretation of somatic mutations in candidate tumor-suppressor genes.
authors.affiliation: Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Wang
authors.forename: Carlo
authors.initials: C
authors.lastname: Rago
authors.forename: Natalie
authors.initials: N
authors.lastname: Silliman
authors.forename: Janine
authors.initials: J
authors.lastname: Ptak
authors.forename: Sanford
authors.initials: S
authors.lastname: Markowitz
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D016208:Databases, Factual; D006801:Humans; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D014407:Tumor Cells, Cultured