Journal Article

The genomic landscape of Mongolian hepatocellular carcinoma

Wang, Xin Wei, Tovuu, Lkhagva-Ochir, Tudev, Undarmaa, Forgues, Marshonna, Budhu, Anuradha, Bayarsaikhan, Enkhjargal, Tandon, Mayank, Chinburen, Jigjidsuren, Candia, Julián, Lack, Justin, Chao, Ann

2020

Overview

Mongolia has the highest incidence of hepatocellular carcinoma (HCC) in the world, but its causative factors and underlying tumor biology remain unknown. Here, we describe molecular characteristics of HCC from 76 Mongolian patients by whole-exome and transcriptome sequencing. We present a comprehensive analysis of mutational signatures, driver genes, and molecular subtypes of Mongolian HCC compared to 373 HCC patients of different races and ethnicities and diverse etiologies. Mongolian HCC consists of prognostic molecular subtypes similar to those found in patients from other areas of Asia, Europe, and North America, as well as other unique subtypes, suggesting the presence of distinct etiologies linked to Mongolian patients. In addition to common driver mutations (TP53, CTNNB1) frequently found in pan-cancer analysis, Mongolian HCC exhibits unique drivers (most notably GTF2IRD2B, PNRC2, and SPTA1), the latter of which is associated with hepatitis D viral infection. These results suggest the existence of new molecular mechanisms at play in Mongolian hepatocarcinogenesis. Mongolia has the highest incidence of—and mortality from—hepatocellular carcinoma (HCC) in the world. Here, the authors examine the genomic and transcriptomic landscape of Mongolian HCC, uncover novel driver mutations, and suggest distinct disease etiologies.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/23 / 45/91 / 631/208/191/2018 / 631/67/1504/1610/4029 / 631/67/69 / Aged / Biomarkers, Tumor - genetics / Cancer / Carcinogenesis - genetics / Carcinoma, Hepatocellular - epidemiology / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - surgery / Carcinoma, Hepatocellular - virology / DNA Mutational Analysis / Etiology / Exome Sequencing / Female / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Hepatectomy / Hepatitis / Hepatitis D - epidemiology / Hepatitis D - genetics / Hepatitis D - surgery / Hepatitis D - virology / Hepatitis Delta Virus - isolation & purification / Hepatocellular carcinoma / Humanities and Social Sciences / Humans / Incidence / Liver - pathology / Liver - surgery / Liver - virology / Liver cancer / Liver Neoplasms - epidemiology / Liver Neoplasms - genetics / Liver Neoplasms - surgery / Liver Neoplasms - virology / Male / Middle Aged / Molecular modelling / Mongolia - epidemiology / multidisciplinary / Mutation / p53 Protein / Prognosis / Science / Science (multidisciplinary)