Abstract 3394: Diagnosis of intrahepatic metastasis (IM) and multi-entric (MC) carcinogenesis by novel mutational signature in patients with multiple and recurrent hepatocellular carcinomas

Abstract

Abstract Hepatocellular carcinoma is a common solid tumor worldwide and represents the third leading cause of cancer death. Patients with hepatocellular carcinoma (HCC) have poor prognosis because of frequent multi-centric (MC) and intrahepatic metastasis (IM). The discrimination between MC and IM is profoundly important for interpreting tumorigenesis and treatment decision making. However, it is difficult to correctly estimate by histological. Previous studies suggest that HBV integration sites, mitochondrial D-loop mutations, microsatellite loss of heterozygosity (MSI LOH) may provide more accurate information. Paired two tumor lesions and adjacent non-tumor tissues from 10 HBV-position patients were collected for whole genome sequencing. The proportion of shared somatic SNV among the tumor lesions was used to separate MC and IM groups. 4 of 10 patients with shared mutation rate higher than 10% (15.89-49.48%) were identified as IMs. 6 patients with shared mutation rate lower than 10% (0.33-1.97%) were identified as MCs. We also used shared HBV integration rate, mitochondrial D-loop, MSI LOH, diameter ratio to identify IM and MC. The coincidence rates between shared mutation rate and shared HBV integration rate, mitochondrial D-loop, MSI LOH, diameter ratio is 88.89%, 77.78%, 88.89%, and 90%, respectively. It suggests that the diameter ratio of multiple HCCs provide a no-invasion method in clonality analysis. Finally, we developed a panel covering 1M regions to replace whole-genome sequencing to identify IM and MC. We validated the shared mutation rate of target panel region in another 19 whole-genome sequencing HCC patients with multiple tumor lesions from ICGC. A consistent rate of 94.74% in shared mutation rate between target panel region and whole genome region, indicated that for patients with resectable multiple HCCs, sequencing-based molecular diagnosis using somatic single nucleotide variation information showed higher sensitivity compared to previous techniques. And a smaller size of target panel contains adequate information is more cost-effective approach for clinical decision making. Citation Format: Pinghua Yang, Shilei Bai, Yanpeng Zhang, Zhihao Xie, Zhangjun Cheng, Jie Yang, Jun Li, Jiaqian Wang, Zhengqing Lei, Yong Xia, Kui Wang, Zheng Li, Baohua Zhang, Xuying Wan, Mengchao Wu, Feng Shen. Diagnosis of intrahepatic metastasis (IM) and multi-entric (MC) carcinogenesis by novel mutational signature in patients with multiple and recurrent hepatocellular carcinomas [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 3394.