Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
General Laboratory Department, National Cancer Center, Ulaanbaatar, Mongolia.
Nat Commun. 2020 Sep 1;11(1):4383. doi: 10.1038/s41467-020-18186-1.
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.
蒙古国是世界上肝细胞癌（HCC）发病率最高的国家，但导致其发病的因素及其潜在的肿瘤生物学机制尚不清楚。在这里，我们通过全外显子组和转录组测序，对 76 名蒙古 HCC 患者的分子特征进行了描述。我们对蒙古 HCC 的突变特征、驱动基因和分子亚型与来自不同种族、不同病因的 373 名 HCC 患者进行了全面的分析。蒙古 HCC 包含与来自亚洲、欧洲和北美的其他地区以及其他独特亚型的患者相似的预后分子亚型，这表明存在与蒙古患者相关的不同病因。除了在泛癌分析中经常发现的常见驱动突变（TP53、CTNNB1）外，蒙古 HCC 还表现出独特的驱动基因（尤其是 GTF2IRD2B、PNRC2 和 SPTA1），后者与丁型肝炎病毒感染有关。这些结果表明，在蒙古肝癌发生中存在新的分子机制。
