It concludes that most cancers exhibit a mutator phenotype as normal mutation rates are insufficient to account for the multiple mutations observed in human tumors.
Anti-mutator mutants, with lower than normal mutation rates, have been observed in bacteria [32], in the phage T4 [33], and in RNA viruses evolving in the presence of mutagens [34].
To test the efficiency of each nucS allele to restore normal mutation rates, the plasmids pMV361 carrying the mutated alleles were integrated in M. smegmatis ΔnucS chromosome.
The obtained results show that the α-stable mutation delivers more solutions than the classical normal mutation within a slightly better time budget.
Michele Cargill, a geneticist at Celera Diagnostics in Alameda, California, and her colleagues examined 7600 genes shared by chimps, humans, and mice, identifying those that had more than the expected number of base changes, given the normal mutation rates in each species.
We proposed that deviations from the normal mutation-purifying selection-drift regime may allow such alleles to persist in the population.
Most epithelial cancers arise from this normal mutation rate.
Whereas the accumulation of sufficient numbers of driver mutations might be highly unlikely with normal mutation rates [ 38], new experimental data illustrate that colorectal cancer mutation frequencies are relatively low and consistent with normal mutation and division rates [ 3].
Normal mutation rates are thus quite sufficient to explain the crucial mutations needed to drive tumorigenesis, but how many mutations exist within a typical cancer?
