Genomic crossroads between non-Hodgkin's lymphoma and common variable immunodeficiency

Area of Science:

• Genomics and Immunology
• Cancer Biology
• Primary Immunodeficiency

Background:

• Common Variable Immunodeficiency (CVID) is a primary immunodeficiency linked to infections, autoimmunity, and cancers like Non-Hodgkin's Lymphoma (NHL).
• NHL can arise from chronic infections, suggesting a potential link to CVID phenotypes.
• Germline variants in CVID may influence somatic mutations in malignancies, hinting at shared underlying mechanisms.

Purpose of the Study:

• To investigate the shared genomic underpinnings between CVID and NHL.
• To characterize the CVID immunodeficiency phenotype within NHL by analyzing common genetic alterations.

Main Methods:

• An in-silico analysis of publicly available datasets from cBioPortal.
• Interrogation of genetic variants in a panel of 50 genes associated with CVID.
• Analysis of 1,309 NHL samples for CVID-associated gene alterations.

Main Results:

• 25% of analyzed NHL samples (323/1,309) exhibited variants within the CVID spectrum.
• PIK3CD (6%) and STAT3 (4%) were the most recurrently altered genes in NHL.
• Pathway analysis revealed enrichment in inflammatory responses, immune surveillance, and DNA repair defects, common to both CVID and NHL.

Conclusions:

• Identified common genomic alterations between CVID and NHL, suggesting shared etiological pathways.
• PIK3R1 emerged as a central node in protein interaction networks, linking CVID and NHL.
• Further research is needed to elucidate the role of genetic variants in CVID and their somatic reflections in NHL for improved diagnostics and therapeutics.