Clinical significance of the ubiquitin ligase UBE3C in hepatocellular carcinoma revealed by exome sequencing

• DOI: 10.1002/hep.27012
• Publication Date: 2014-01-15T09:20:55Z
• Authors: Jia-Hao Jiang; Yan-Feng Liu; Ai-Wu Ke; Fang-Ming Gu; Yao Yu; Zhi Dai; Qiang Gao; Guo-Ming Shi; Bo-Yi Liao; You-Hua Xie; Jia Fan; Xiao-Wu Huang; Jian Zhou
• Keywords: Exome

Virus-induced hepatocarcinogenesis involves a series of histological developmental processes with the stepwise acquisition several genetic changes that are necessary for malignant transformation hepatocytes. Although alterations known to be involved in pathogenesis hepatocellular carcinoma (HCC), little is about contributions specific genes this process. To gain insight into neoplastic evolution from chronic hepatitis B virus infection dysplastic nodules (DN) HCC, we captured and sequenced exomes four DNA samples: one DN sample, two HCC samples, control peripheral blood sample single patient. Mutations UBE3C gene (encoding ubiquitin ligase E3C) were observed both tumor tissues. Then resequenced cohort 105 patients identified mutations 17 out total 106 (16.0%) patients. The subsequent experiments showed promoted progression by regulating cells epithelial-mesenchymal transition. Clinically, tissue microarray study containing 323 revealed overexpression primary tissues correlated decreased survival (hazard ratio [HR] = 1.657, 95% confidence interval [CI] 1.220-2.251, P 0.001) early recurrence (HR 1.653, CI 1.227-2.228, postoperative Conclusion : Our findings indicate candidate oncogene development therefore potential therapeutic target applicable (Hepatology 2014;59:2216–2227)