Sequencing analysis of Helicobacter pylori infection in gastric mucosa and its progression to gastric mucosa-associated tissue (MALT) lymphoma

IntroductionThe pathogenesis of gastric mucosa-associated tissue (MALT) lymphoma is associated with Helicobacter pylori infection. Although treatment strategies and responsiveness according to the stage of gastric MALT lymphoma have been widely reported, a detailed study of the biological carcinogenic process is still required. MethodPaired, fresh tumor-adjacent normal and gastric mucosal tissue samples from 13 patients with gastric MALT lymphoma were prospectively collected. Whole exome sequencing (WES) and whole-transcriptome sequencing (WTS) data were generated. The analysis of mutations, gene fusion, gene expression, and the microbiome was stratified by H. pylori infection and disease status. ResultsSomatic mutations in TRAF3 and TNFAIP3 were identified in H. pylori-negative gastric MALT lymphoma. Fusions involving BIRC3-MALT1 (2 samples) and TBL1XR1-TP63 (1 sample with H. pylori infection) were detected. Stepwise comparative analysis of RNA expression revealed upregulation of immune response, inflammatory responses, and the NF- {kappa}B signaling pathway in H. pylori-positive MALT lymphoma cases. Pathways associated with pathogens were upregulated in H. pylori-negative MALT lymphoma cases, suggesting that infections other than H. pylori may affect lymphomagenesis. Microbiome analysis revealed that genus_Rothia was negatively correlated with alpha diversity. ConclusionA stepwise approach using diverse stages of WTS data revealed detailed pathogenic mechanisms of gastric MALT lymphoma. Chronic inflammation following infection contributes to gastric MALT lymphomagenesis in both H. pylori positive and negative cases.