Mutational landscape of gastric extranodal marginal zone lymphoma according to Helicobacter pylori status

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is an antigen-driven malignancy in which Helicobacter pylori ( H. pylori ) eradication achieves remission in most localized cases, yet the genomic underpinnings of biological heterogeneity across H. pylori subgroups remain poorly defined. We performed targeted next-generation sequencing on formalin-fixed paraffin-embedded tumor tissue from 28 patients with stage IE gastric MALT lymphoma, classified as H. pylori -negative (HPN; n = 8) or H. pylori -positive (HPP; n = 20). Recurrently altered genes were grouped into three functional categories: epigenetic and transcriptional regulatory genes, NF-κB signaling-related genes, and immune-related genes. Overall mutational burden was low (median: 1 altered gene per case; range, 0–9), with PTEN , KMT2D , and TET2 as the most frequently mutated genes, distributed across both subgroups. Across the predefined functional categories, epigenetic/transcriptional regulatory alterations were more frequent in HPN cases (62.5% vs. 30.0%), with NCOR1 and ZFHX3 detected only in this group. NF-κB-related alterations were comparable between groups (12.5% vs. 15.0%). Immune-related alterations ( B2M , CD274 ) were observed only in HPP cases (0.0% vs. 20.0%). No differences reached statistical significance. Gastric MALT lymphoma harbors a shared low mutational burden across H. pylori subgroups, with modest differences in recurrent mutation profiles that did not reach statistical significance.