This is a review on mutational signatures that reflect the exogenous and endogenous origins of genetic damage as well as the capacity of hepatobiliary cells to repair and replicate DNA. The diversity of mutagenic processes active in hepatobiliary cancers highlights a prominent source of the heterogeneity that is observed clinically. However, a substantial proportion of mutational signatures detected in hepatocellular carcinoma and biliary tract cancer remain of unknown cause, emphasizing the important contribution of processes yet to be identified. Exploiting mutational signatures to retrospectively understand hepatobiliary carcinogenesis could advance preventative management of these tumors as well as potentially predict treatment response and guide the development of therapies targeting tumor evolution.

(Zhuravleva, E., et al. – Nat Rev Gastroenterol Hepatol, March 2022)

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