Human cancers express mutator phenotypes: origin, consequences and targeting

Abstract

The mutator phenotype describes a process by which tumour cells are proposed to evolve genetic alterations that contribute to the acquisition of the various attributes that are required for tumour progression. Here, Lawrence Loeb updates this hypothesis, focusing on how DNA sequencing has informed the current view of the mutator phenotype in cancer. Recent data on DNA sequencing of human tumours have established that cancer cells contain thousands of mutations. These data support the concept that cancer cells express a mutator phenotype. This Perspective considers the evidence supporting the mutator phenotype hypothesis, the origin and consequences of a mutator phenotype, the implications for personalized medicine and the feasibility of ablating tumours by error catastrophe.