For cooperative lineage expansion with C D<3, non-mutator pathways, or mutator pathways with early mutator mutations, are more likely pathogenic mechanisms.
Mutator mutations are more likely to occur early, and to occur when more oncogenic mutations are required to create a tumor.
For constant fitness models, negative clonal selection models, and incremental lineage expansion models, mutator mutations are more efficient if they occur early.
MSH2 is frequently mutated in HNPCC/LS, while MSH6 mutations are more rare (although MSH6, like MSH3, is also commonly frame-shifted in MSI positive CRCs [ 52, 54]).
In MDSs, U2AF1 mutations are more frequent in ASXL1-mutated than in ASXL1-wildtype cases [ 38, 42].
Thereby, a mechanism evolves where structure biases the mutational distribution in a way that the positive effects of mutations are more likely.
The mutations are more prevalent in the most far-flung populations, like Indian tribes in South America descended from the neophiliacs who crossed the Bering Strait.
Smaller mutations are more common and include point mutations, in which substitution of a single nucleotide base occurs, and deletion or insertion mutations, which involve several bases.
Somatic mutations are more common, and might account for malignant transformation of sporadic tumors.
SDHB and SDHD mutations are more common, whereas SDHA and SDHC mutations are rare.
In addition, smaller tumors (<4 cm) with PBRM1 mutations are more likely to exhibit stage II pathologic features.
