Defining relative mutational difficulty to understand cancer formation.

ABSTRACT: Most mutations in human cancer are low-frequency missense mutations, whose functional status remains hard to predict. Here, we show that depending on the type of nucleotide change and the surrounding sequences, the tendency to generate each type of nucleotide mutations varies greatly, even by several hundred folds. Therefore, a cancer-promoting mutation may appear only in a small number of cancer cases, if the underlying nucleotide change is too difficult to generate. We propose a method that integrates both the original mutation counts and their relative mutational difficulty. Using this method, we can accurately predict the functionality of hundreds of low-frequency missense mutations in p53, PTEN, and INK4A. Many loss-of-function p53 mutations with dominant negative effects were identif

SUBMITTER: Shan L 

PROVIDER: S-EPMC7371891 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature