Abstract 3535: Identification of multiple hepatocellular carcinoma using genomic approach

Abstract

Multiple hepatocellular carcinoma (HCC) is categorized into two types; multicentric hepatocarcinogenesis (MC) and intrahepatic metastasis (IM). Although clinical discrimination of the types of multiple HCC has been proposed, it is quite difficult to determine it correctly even after histological diagnosis. In order to diagnose multiple HCC as MC or IM, we compared pairs of multiple HCC samples from 60 patients with multiple HCC and 2 patients with pairs of primary HCC and extrahepatic metastasis such as adrenal grand and lung metastasis with regard to molecular aberrations. Exome or capture sequences showed that more than 70% of somatic mutations were common in the pairs of IM, which were consistent with the result of a pair of primary HCC and extrahepatic metastasis, while no common somatic mutations was detected in genomic MC pairs. Notably, more than 60% of patients who were clinically diagnosed metachronous MC were genetically IM due to the concordance of mutation and shows significantly frequent tumor thrombus, suggesting that genomic IM pairs developed from the common ancestor. Epigenetically, methylation profiles were similar in a pair of IM, while those of MC were different each other. Consequently the accuracy of clinical diagnosis of multiple HCC was only 53.3%. In addition, cell-free DNA was analyzed using exome sequence in five patients with recurrent HCC, and found that somatic mutations of cell free DNA were similar to the primary HCC only in genomic IM but not in genomic MC cases. Intriguingly, overall survivals of patients with clinical IM was significantly shorter than those with clinical MC, while overall survivals of patients with genomic IM and genomic MC were almost similar. Taken together, comparison of mutations in a pair of HCCs makes it possible to classify multiple HCC into MC and IM, which is difficult to be correctly determined in clinical practice. In addition our data showed that it is not clinically important to determine the types of multiple HCC. Furthermore liquid biopsy for mutation analysis is available to make treatment plans for multiple HCC patients. Citation Format: Yutaka Midorikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Tadatoshi Takayama, Hiroyuki Aburatani. Identification of multiple hepatocellular carcinoma using genomic approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3535.