Genetic Characterization and Clinical Features of <i>Helicobacter pylori</i> Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

• Main Authors: Barbara Kiesewetter, Christiane Copie-Bergman, Michael Levy, Fangtian Wu, Jehan Dupuis, Caroline Barau, Luca Arcaini, Marco Paulli, Marco Lucioni, Arturo Bonometti, Antonio Salar, Concepción Fernández-Rodriguez, Miguel A. Piris, Francesco Cucco, Rachel Dobson, Yan Li, Zi Chen, Cyrielle Robe, Ingrid Simonitsch-Klupp, Andrew Wotherspoon, Markus Raderer, Ming Qing Du
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Cancers
• Subjects: extranodal lymphoma 1; MALT lymphoma 2; Helicobacter pylori 3; NF-κB pathway 4
• Online Access: https://www.mdpi.com/2072-6694/13/12/2993

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, <i>H. pylori</i> negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of <i>H. pylori</i> negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: <i>MALT1</i> translocation, most likely t(11;18)(q21;q21)/<i>BIRC3-MALT1,</i> was detected in 39% (22/57) cases, and <i>IGH</i> translocation was further seen in 12 <i>MALT1</i>-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (<i>TNFAIP3</i> = 23%, <i>CARD11</i> = 9%, <i>MAP3K14</i> = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from <i>MALT1</i>, albeit not <i>IGH</i> translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (<i>p</i> = 0.004). Conclusion: <i>H. pylori</i> negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.