Abstract 163: Genetic difference between multicentric carcinogenesis and intrahepatic metastasis of hepatocellular carcinoma

Abstract

Abstract Multiple hepatocellular carcinoma (HCC) is categorized into 2 types; multicentric hepatocarcinogenesis (MC) and intrahepatic metastasis (IM). Although discrimination of the types of multiple HCC is of clinical importance, it is quite difficult to determine it correctly even after histological diagnosis. In order to classify multiple HCC into MC and IM, we compared pairs of multiple HCC samples from 12 patients who were clinically diagnosed MC, 6 patients with IM with regard to molecular aberrations, and 2 patients with pairs of primary HCC and extrahepatic metastasis such as adrenal grand and lung metastasis. Exome sequence showed that 125 mutations (90.6%) per patient with IM were common, which were consistent with the result of a pair of primary HCC and extrahepatic metastasis. On the other hand, 138 somatic mutations per tumor, and no common somatic mutations were identified in the 7 patients with MC. Especially only a few passenger mutations were different between IM specimens suggesting that IM pairs developed from the common ancestor. In contrast, 5 patients who clinically diagnosed MC had common mutations (41.7%), which indicates that pairs of HCC of these patients were genetically IM. Notably, mutation signatures obtained from exome sequence data of 2 nodules from the same patients with IM were similar, while those from patients with MC were different by profiling analysis. On the other hand, methylation profile shows that 2 HCC samples from the same patients with MC as well as IM were classified into the same cluster; the methylation status from the different ancestor is similar, and not altered through carcinogenesis. Taken together, comparison of mutations in a pair of HCCs makes it possible to classify multiple HCCs into MC and IM, which is difficult to be correctly determined in clinical practice, and is available to make treatment plans for multiple HCC patients. Furthermore, methylation status of 2 nodules of MC from same patient were similar, while those of mutation signatures were different, which suggests that the epigenomic changes are the earlier event prior to the genomic alterations. Citation Format: Yutaka Midorikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shingo Tsuji, Genta Nagae, Tadatoshi Takayama, Hiroyuki Aburatani. Genetic difference between multicentric carcinogenesis and intrahepatic metastasis of hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 163.