Genomic clustering of fitness-affecting mutations favors the evolution of chromosomal instability.

ABSTRACT: Most solid cancers are characterized by chromosomal instability (CIN)-an elevated rate of large-scale chromosomal aberrations and ploidy changes. Chromosomal instability may arise through mutations in a range of genomic integrity loci and is commonly associated with fast disease progression, poor prognosis, and multidrug resistance. However, the evolutionary forces promoting CIN-inducing alleles (hereafter, CIN mutators) during carcinogenesis remain poorly understood. Here, we develop a stochastic, individual-based model of indirect selection experienced by CIN mutators via genomic associations with fitness-affecting mutations. Because mutations associated with CIN affect large swaths of the genome and have the potential to simultaneously comprise many individual loci, we show that indirec

SUBMITTER: Raynes Y 

PROVIDER: S-EPMC6346662 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature