Abstract 5439: Distinct genomic profile in H. pylori associated gastric cancer

Abstract

Abstract Background: Gastric cancer is one of the most common and deadly cancer types. Currently 4 subtypes have been identified with unique molecular alterations: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI), chromosomal instability (CIN), and genomic stable (GS) tumors. However, many gastric tumors are associated with the bacterium Helicobacter pylori but the genomic landscape of this subgroup of tumors remains largely unknown. Methods: Targeted-sequencing covering 425 genes were performed retrospectively on 1759 gastric tumor tissues and matched normal blood samples. The mean sequencing depth of tumors was 1159X. Nonsynonymous mutations, copy-number variation (CNV) and MSI status were called from human DNA reads; non-human DNA reads were mapped to NCBI microbial reference genome using Kraken and significant species were identified. Results: Overall, 37 (2.67%) samples were EBV-positive, 200 (11.37%) samples were H. pylori-positive, and 10 (0.57%) samples were positive for both. Other notable species identified in tumor samples were E. coli and C. acnes. No bacteria or viral reads were found in normal blood. Among the rest, 59 (3.35%) samples were MSI, 380 (21.6%) were CIN, and 1017 (57.82%) were GS. H. pylori-positive samples tend to be GS (85.5%, p < 0.001) and microsatellite stable (95%, p = 0.04). The most common mutations identified in H. pylori-positive tumors were TP53 (47%), CDH1 (12%) and ARID1A (8.5%). The top CNV events were amplification in MCL1 (14.5%), TERC (9%), CCNE1 (8.5%), PTPRD (8.5%), and MYC (7.5%). Compared to other GS tumors, mutation in AKT3 (p = 0.002) and amplification of TERC (p = 0.008) as well as MCL1 (p = 0.0.029) were significantly enriched in H. pylori-positive tumors. There was no difference in patients' sex or age among subtypes (p >= 0.05). Conclusion: This study characterized the genomic landscape of H. pylori positive gastric tumors using targeted-sequencing, which allowed direct comparison with other subtypes of gastric cancer. Identification of DNA reads from infectious agents in the tumor samples indicates that deep sequencing platform has promising utility in uncovering the characteristics of microbial environment of tumor. Co-infection between H. pylori and EBV occurred at a low frequency. H. pylori-positive tumors were GS and microsatellite stable with unique molecular features. Future study examining difference in treatment response among these subtypes of gastric cancer are warranted. Citation Format: Ao Wang, Hua Bao, Pengfei Hu, Yong Wu, Jinfeng Zhang, Xue Wu, Xiaonan Wang, Yang Shao. Distinct genomic profile in H. pylori associated gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5439.