Supplementary Figure from Hepatocellular Carcinoma in Mongolia Delineates Unique Molecular Traits and a Mutational Signature Associated with Environmental Agents
Funding
Instituto de Salud Carlos III (ISCIII)
Departament d'Empresa i Coneixement, Generalitat de Catalunya (Ministry of Business and Knowledge, Government of Catalonia)
Generalitat de Catalunya (Government of Catalonia)
Gilead Research Scholars (GRS)
Samuel Waxman Cancer Research Foundation (SWCRF)
Bristol-Myers Squibb (BMS)
Asociación Española para el Estudio del Hígado (AEEH)
Deutsche Forschungsgemeinschaft (DFG)
U.S. Department of Defense (DOD)
Tisch Cancer Institute Grant
Institut National de la Santé et de la Recherche Médicale (Inserm)
Labex OncoImmunology Investissement d'Avenir
Equipe labellisee par la Ligue Nationale Contre le Cancer
Ministerio de Ciencia e Innovación (MICINN)
National Institutes of Health (NIH)
Cancer Research UK (CRUK)
Fundación Científica Asociación Española Contra el Cáncer (AECC)
Fondazione AIRC per la Ricerca sul Cancro
ARTICLE ABSTRACT
Mongolia has the world's highest incidence of hepatocellular carcinoma (HCC), with ∼100 cases/100,000 inhabitants, although the reasons for this have not been thoroughly delineated.
We performed a molecular characterization of Mongolian (n = 192) compared with Western (n = 187) HCCs by RNA sequencing and whole-exome sequencing to unveil distinct genomic and transcriptomic features associated with environmental factors in this population.
Mongolian patients were younger, with higher female prevalence, and with predominantly HBV–HDV coinfection etiology. Mongolian HCCs presented significantly higher rates of protein-coding mutations (121 vs. 70 mutations per tumor in Western), and in specific driver HCC genes (i.e., APOB and TSC2). Four mutational signatures characterized Mongolian samples, one of which was novel (SBS Mongolia) and present in 25% of Mongolian HCC cases. This signature showed a distinct substitution profile with a high proportion of T>G substitutions and was significantly associated with a signature of exposure to the environmental agent dimethyl sulfate (71%), a 2A carcinogenic associated with coal combustion. Transcriptomic-based analysis delineated three molecular clusters, two not present in Western HCC; one with a highly inflamed profile and the other significantly associated with younger female patients.
Mongolian HCC has unique molecular traits with a high mutational burden and a novel mutational signature associated with genotoxic environmental factors present in this country.
