83P - Comparing clonality between components of combined hepatocellular carcinoma and cholangiocarcinoma by targeted sequencing

Abstract

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a very rare tumor. It has two different components (hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC)) in a single mass. Although several studies have determined genetic characteristics of cHCC-CC, Next-generation sequencing (NGS) data for comparing clonality of cHCC-CC are currently unavailable. Methods: We selected four cHCC-CC cases and micro-dissected HCC, CC, and normal components separately from each case. DNA and RNA were isolated from each sample and sequenced by Oncomine Comprehensive Panel (OCP) interrogating 143 cancer genes using Ion S5 XL sequence platform. Genetic features of HCC and CC from each patient were compared. Results: All cases successfully produced NGS data. Two cases demonstrated different mutations between HCC and CC components (biclone) while two cases shared the same mutations between two components (monoclone). SNPs of TP53 (4/4) and PTEN (1/4) and gene amplifications of MET (1/4), c-MYC (1/4), and CDK6 (1/4) were found in CC component. In HCC component, SNPs of TP53 (3/4), PTEN (1/4) and CTNNB1 (1/4) and CCND1 amplification (1/4) were detected. Two biclonal cases showed histologically distinguished border between HCC and CC components with or without intermediate cell foci. Two monoclonal cases showed histologically ambiguous border between HCC and CC components with more intermingled pattern than biclonal cases. Conclusions: We compared genetic compositions of HCC and CC components and matched clonality with histologic feature in cHCC-CC using targeted sequencing. Two (50%) of four cases had different clones between HCC and CC components with more distinguished histologic features than monoclonal cases. Considering such heterogeneity, partly sequencing is recommended for cHCC-CC, especially in those who have histologically distinguished HCC and CC components regardless of the presence of intermediate component. Legal entity responsible for the study: Nara Yoon. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.