Mutational Processes in Hepatocellular Carcinoma: The Story of Aristolochic Acid

Semin Liver Dis DOI: 10.1055/s-0039-1685516Each hepatocellular carcinoma displays dozens of mutations in driver and passenger genes. The analysis of the types of substitutions and their trinucleotide context defines mutational signatures that recapitulate the endogenous and exogenous mutational processes operative in tumor cells. Aristolochic acid is present in plants from the genus Aristolochia and causes chronic nephropathy. Moreover, aristolochic acid has genotoxic properties responsible for the occurrence of urothelial carcinoma. Metabolites of aristolochic acid form DNA adducts on adenine residues leading to a specific mutational signature with almost exclusively A:T to T:A transversions, preferentially in a CTG trinucleotide context. Interestingly, this mutational fingerprint has been identified in a subset of hepatocellular carcinomas suggesting that aristolochic acid is a new risk factor for hepatocellular carcinoma. More data are warranted to capture the real impact of exposure to aristolochic acid in hepatocellular carcinoma occurrence worldwide. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research