Fundamental immune-oncogenicity trade-offs define driver mutation fitness.

ABSTRACT: Missense driver mutations in cancer are concentrated in a few hotspots¹. Various mechanisms have been proposed to explain this skew, including biased mutational processes², phenotypic differences^3-6 and immunoediting of neoantigens^7,8; however, to our knowledge, no existing model weighs the relative contribution of these features to tumour evolution. We propose a unified theoretical 'free fitness' framework that parsimoniously integrates multimodal genomic, epigenetic, transcriptomic and proteomic data into a biophysical model of the rate-limiting processes underlying the fitness advantage conferred on cancer cells by driver gene mutations. Focusing on TP53, the most mutated gene in cancer¹, we present an inference of mutant p53 concen

SUBMITTER: Hoyos D 

PROVIDER: S-EPMC9159948 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature