Semin Liver Dis
DOI: 10.1055/s-0039-1685516
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mutational Processes in Hepatocellular Carcinoma: The Story of Aristolochic Acid

Jean-Charles Nault
1  Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors laboratory, Paris, France
2  Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
3  Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France
,
Eric Letouzé
1  Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors laboratory, Paris, France
› Author Affiliations
Further Information

Publication History

Publication Date:
30 April 2019 (eFirst)

Abstract

Each 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.