Endogenous mutagenesis and cancer.
Mutations in DNA accrue relentlessly, largely via stochastic processes. Random changes accumulate, eventually disabling genetic components which result in the formation of the cancer phenotype. Given the infrequency of measured nucleotide changes and the requirement for several mutations to occur in the same cell, it has been postulated that the rate of mutation must become elevated early in the course of evolution of the cancer. Recently, large scale sequencing of tumor DNA has sought to directly measure random mutations. We discuss the implications of these findings and the factors that must be considered in order for fruitful determination of whether a mutator phenotype is a necessary precursor for cancer.
Davidson
John F
JF
Department of Pathology, The Joseph Gottstein Memorial Cancer Research Laboratory, University of Washington, Seattle, WA 98195, USA.
Guo
Haiwei H
HH
Loeb
Lawrence A
LA
D001483:Base Sequence; D002869:Chromosome Aberrations; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010641:Phenotype