Abstract 3794: Understanding H. pylori-related gastric MALToma using multi-omics data
Authors: Song Hyojin , Kang Eun Ae , Soh Hosim , Lee Sungyoung , Yun Hongseok , Chung Hyunsoo , Chun Jaeyoung , Yoon Sung-Soo , Koh Youngil 
Published: August 2019

Abstract
Mucosa-associated lymphoid tissue lymphoma (MALToma) is an extranodal B cell lymphoma, predominantly associated with bacterial infection of the stomach by Helicobacter pylori (H. pylori). Infection of H. pylori can be divided into four steps: 1) entrance into host and survival; 2) motility and chemotaxis; 3) Interaction between adhesion-receptors and colonization, and 4) release of toxins and damage to host. To date, pathogenesis of bacteria related lymphoma and individual functions of H. pylori genes are not yet unearthed. Hence, we aim to characterize the carcinogenic mechanism of H. pylori-related MALToma throughout this study.We obtained fresh gastric tissues of both tumor and adjacent normal region from MALToma patients. Using the tissue and saliva samples, we generated 12 sets of whole exome and transcriptome sequencing data. To identify the gene expression pattern, we aligned the raw data using STAR algorithm and quantified expression of genes in both H. pylori and human genome. Next, we estimated the relative abundance of immune cells in each tissue, employing a linear support vector regression (SVR) based analytical algorithm, CIBERSORT. Besides, we investigated somatic mutations in the patients using our internal pipeline.Gene expression profiling of H. pylori enabled us to identify frequently expressed genes in MALToma, and among them, aliphatic amidase (aimE) was expressed in 9 of 21 lesion tissues. The role of aimE is to contribute to ammonia production, which is analogous to that urease. Then, we explored gene expression pattern of immune checkpoint modulators. We determined that major groups of high CD112, CD155, and VISTA expression, and minor groups of high CD86 and PD-L1 expression, signifying cell adhesion and regulation of T cell activation.From CIBERSORT data, we found that increment of resting CD4 memory T cells and decrease of plasma cells in pair-wise MALToma donors. Since CD4+ T cells are abundantly distributed in the gastric cellular infiltrates, this immune cell composition implies that CD4 memory T cells might have been re-activated by exposure to bacterial antigens. In addition, majority of B cells including plasma cells die after they fight against infected cells, and this supports the decreased plasma cells in the tumor tissues.Using exome sequencing data, we identified two recurrent missense mutations (K169R and N175S) of a cell cycle gene, CDC27, in ~20% of MALToma patients. across the donors. Previous studies mentioned that impaired functions of CDC27 facilitate cell growth as it fails to regulate the cell growth inhibition.To understand carcinogenesis of H. pylori-related MALToma, we focused on determining gene expression patterns, immune cell composition, and recurrent somatic mutations. In conclusion, we demonstrated expression profiling of both H. pylori genes and human checkpoint modulators, estimation of immune cell abundance, and verification of recurrent DNA mutations, in MALToma.
Citation Format: Hyojin Song, Eun Ae Kang, Hosim Soh, Sungyoung Lee, Hongseok Yun, Hyunsoo Chung, Jaeyoung Chun, Sung-Soo Yoon, Youngil Koh. Understanding H. pylori-related gastric MALToma using multi-omics data [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 3794.