Mutational Processes in Hepatocellular Carcinoma: The Story of Aristolochic Acid

Jean-Charles Nault; Eric Letouzé

doi:10.1055/s-0039-1685516

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2019; 39(03): 334-340
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

¹Centre 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

²Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France

³Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France

,

Eric Letouzé

¹Centre 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

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.

Keywords

liver cancer - kidney - carcinogen

Full Text

References

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