Mutator Phenotype

Definition

Mutator phenotype refers to the increase in mutation rate of cancer cells. The Mutator Phenotype Hypothesis was formulated to account for the disparity between the infrequency of spontaneous mutations in normal cells and the large numbers of mutations observed in human tumors. The hypothesis states that an increase in mutation rate is an early event in tumorigenesis. Some of the random mutations produced throughout the genome are located in genes that normally function to guarantee the accurate transfer of genetic information with each cell division. The expression of this “mutator phenotype” leads to a cascade of mutations throughout the genome including mutations in other genes required for the maintenance of genetic stability. Among the many mutations produced are ones that promote growth, invasion, and metastasis, the hallmarks of cancer.

Mutator Phenotype. Fig. 1

Accumulation of mutations during tumor proliferation. As each cancer enlarges, it encounters barriers to...