title: Multiple mutations and cancer.
abstract: Most human tumors are highly heterogenous. We have hypothesized that this heterogeneity results from a mutator phenotype. Our premise is that normal mutation rates are insufficient to account for the multiple mutations found in human cancers, and, instead, that cancers must exhibit a mutator phenotype early during their evolution. Here, we examine the current status and implications of the mutator phenotype hypothesis for the prognosis, treatment, and prevention of human cancers.
authors.affiliation: Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195-7705, USA. laloeb@u.washington.edu
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Loeb
authors.forename: Keith R
authors.initials: KR
authors.lastname: Loeb
authors.forename: Jon P
authors.initials: JP
authors.lastname: Anderson
mesh_terms: D001483:Base Sequence; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D010641:Phenotype