Comparison of mutational landscape of non-alcoholic fatty liver disease, viral hepatitis, and alcohol consumption related hepatocellular carcinoma.

Abstract

e16614 Background: Hepatocellular cancer (HCC) is the seventh most common cancer and the fourth leading cause of cancer-related death worldwide. The most common risk factors of HCC have traditionally included hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol-related liver disease (ALD). Recently, Non-Alcoholic Fatty Liver Disease (NAFLD) has emerged as the fastest growing risk factor for the development of HCC. This study reports the mutation landscape of NAFLD-related hepatocellular carcinoma (HCC) versus other etiologies. Methods: Mutation data of 219 HCC samples were collected from TCGA database, including 13 NAFLD, 87 HBV, 37 HCV, and 82 ALD-related samples. We analyzed mutations for different type of HCC samples using GDC level 3 mutation data. Driver mutations were called by applying software MuSig2CV. Results: In 219 samples, a total of 32189 mutations were identified, including 3163 in NAFLD, 11430 in HBV, 6390 in HCV, and 11206 in ALD-related HCC samples. Driver genes shared by viral hepatitis and ALD-related samples were TP53 (32% for ALD, 33% for HBV, 42% for HCV) and CTNNB1(32 % for HCV, 26% for HBV,29% for ALD), while TP53 was not among the highest frequency of mutations in NAFLD-related samples. As lack of NAFLD-related HCC samples (n = 13), most frequently mutated genes in NAFLD-related HCC samples were computed instead of driver genes. Top 5 mutated genes in NAFLD-related HCC samples were TTN (36%), CACNA1B (27%), DSCAM (27%), GLI2 (27%), and BEB (27%). Conclusions: From our results, TP53 has a lower mutation frequency in NAFLD-related HCC samples than in other types of HCC. To further validate this finding, a larger size of NAFLD-related HCC samples is essential.