Abstract 5119: Genomic landscape analysis in tumor tissue and circulating tumor DNA of Chinese patients with hepatocellular carcinoma

Abstract

Abstract Background: Hepatocellular carcinoma (HCC) is a leading cause of tumor-associated death worldwide, owing to its high 5-year postoperative recurrence rate and heterogeneity. Although Molecular profiling has been used to predict prognosis and guide targeted therapy, obtaining liver tissue biopsies was still a clinical challenge of advanced HCC patients. Circulating tumor DNA (ctDNA) testing as a novel and convenient detecting techniques, which can revealed comprehensive information regarding to tumor genome profiles. The purpose of the study was to analyze and compare the genomic landscape characteristics of tumor tissue and ctDNA in Chinese HCC. Methods: 187 tumor tissue samples and 293 plasma samples from patients with HCC were collected from Nanfang hospital and 3DMed cohort, respectively. Next generation sequencing (NGS) assay (381/733 genes panel) was performed on tumor and plasma samples to capture tumor somatic single-nucleotide variants (SNVs). The gene variants information was summarized, analyzed and visualize using the maftools R package (Mayakonda et al. 2018.). Results: In total, DNA alterations were detected in 93.86% (275/293) plasma samples and 90.91% (170/187) in tumor samples, which variant levels included pathogenic, likely pathogenic and variant of uncertain significance. The most commonly altered genes in ctDNA results were TP53 (52%), TERT (24%), LRP1B (22%), FAT1 (15%), CTNNB1 (14%). While in HCC tumor testing results were TP53 (55%), TERT (27%), CTNNB1 (17%), SPTA1 (14%) and ARID1A (12%). Both the most variant classification was missense, next were frameshift indel. Both the top five affected pathways were TP53, RTK-RAS, NOTCH, WNT and Cell Cycle. In WNT pathway related genes, the highest alteration frequency tumor oncogene was CTNNB1, and suppressor gene was APC. We analyzed mutually exclusive and co-occurring event on top 25 mutated genes. In ctDNA analysis results, the probability of co-mutation between LRP1B and KMT2A gene was the highest (p < 0.001), while mutual exclusion between ARID1A and EGFR gene was the highest. Conclusion: Circulating tumor DNA mutation detection in HCC is feasible in the absence of HCC tissue DNA. The analysis results revealed the genomic landscape characteristics of blood-derived ctDNA in HCC were consistent with tumor tissues, which can provided HCC potential prognosis and treatment related genes information to further study. Citation Format: Dinghua Yang, Sheng Yu, Baitang Guo, Tingting Chen. Genomic landscape analysis in tumor tissue and circulating tumor DNA of Chinese patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5119.