Next generation sequencing of HCC from European and Asian HCC cohorts. Back to p53 and Wnt/beta-catenin

作者：Teufel Andreas^*; Marquardt Jens U; Galle Peter R

来源：Journal of Hepatology, 2013, 58(3): 622-624.

DOI：10.1016/j.jhep.2012.10.006

Hepato cellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copynumber analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID IA, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus (HBV)-related tumors, led to impaired TP53 function. In contrast, inactivation of chromatin remodelers was frequent and predominant in alcoholrelated tumors. Moreover, association of mutations in specific genes (RPS6KA3-AXIN1 and NFE2L2-CTNNB1) suggested that Wnt/,beta-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways. This study provides insight into the somatic mutational landscape in HCC and identifies interactions between mutations in oncogene and tumor suppressor gene mutations related to specific risk factors.

• 出版日期2013-3