Research Papers: Pathology:
Frequent somatic TERT promoter mutations and CTNNB1 mutations in hepatocellular carcinoma
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Seung Eun Lee1, Seong-Hwan Chang2, Wook Youn Kim1, So Dug Lim1, Wan Seop Kim1, Tea Sook Hwang1 and Hye Seung Han1
1 Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
2 Department of Surgery, Konkuk University School of Medicine, Seoul, Korea
Hye Seung Han, email:
Keywords: TERT, CTNNB1, hepatocellular carcinoma, intratumoral genetic heterogeneity, Pathology Section
Received: May 05, 2016 Accepted: September 12, 2016 Published: September 19, 2016
Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma.
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