Abstract 5855: The genomic landscape of Mongolian hepatocellular carcinoma

Abstract

Abstract Mongolia has the highest incidence of-and mortality from- hepatocellular carcinoma (HCC) in the world, which is between three and seven times higher than that observed in other high-incidence populations, such as South Korea, Thailand, and China. In Mongolia, where cancer is the second most common cause of death accounting for nearly a fifth of deaths, HCC is the most prevalent cancer type at about 40% of all cancers. Despite the daunting proportion of this longstanding health crisis, the molecular landscape of Mongolian HCC has not been studied yet. Filling this gap, we aim to identify robust molecular subclasses and driver features informative of the etiology and progression of the disease. Here, we describe molecular characteristics of 76 Mongolian HCC patients by whole-exome and whole-transcriptome sequencing. We present a comprehensive comparison of mutational signatures, driver genes and molecular subtypes of Mongolian HCC versus 373 HCC patients of different ethnicities and diverse etiologies. Mongolian HCC consists of several similar prognostic molecular subtypes in patients from other areas of Asia, Europe and North America as well as several unique types, suggesting potentially the presence of unique etiologies linked to Mongolian patients. Consistently, Mongolian HCC exhibits several common driver mutations (TP53, CTNNB1) frequently found in pan-cancer analyses but also a unique driver (SPTA1) that may be linked to hepatitis D viral infection. Furthermore, unique hotspot missense mutations were identified in driver genes GTF2IRD2B and PNRC2. These results indicate the existence of novel molecular mechanisms at play in Mongolian hepatocarcinogenesis. Citation Format: Julián Candia, Enkhjargal Bayarsaikhan, Mayank Tandon, Anuradha Budhu, Marshonna Forgues, Justin Lack, Ann Chao, Jigjidsuren Chinburen, Xin W. Wang. The genomic landscape of Mongolian hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5855.