Damage and Misrepair Signatures: Compact Representations of Pan-cancer Mutational Processes.

ABSTRACT: Mutational signatures of single-base substitutions (SBSs) characterize somatic mutation processes which contribute to cancer development and progression. However, current mutational signatures do not distinguish the two independent steps that generate SBSs: the initial DNA damage followed by erroneous repair. To address this modelling gap we developed DAMUTA, a hierarchical Bayesian probabilistic model that infers separate signatures for each process, and captures their sample-specific interaction. We applied DAMUTA to 18,974 pan-cancer whole genome sequencing mutation catalogues from 23 cancer types and show that tissue-specificity in mutation patterns is driven largely by variability in damage processes. We also show that misrepair processes are predictive of DNA damage response deficien

SUBMITTER: Harrigan CF 

PROVIDER: S-EPMC12154844 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature