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A gene is known by the company it keeps: enrichment of TNFAIP3 gene aberrations in MALT lymphomas expressing IGHV4‐34 antigen receptors
Author(s) -
Agathangelidis Andreas,
Xochelli Aliki,
Stamatopoulos Kostas
Publication year - 2017
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4982
Subject(s) - ighv@ , biology , chronic lymphocytic leukemia , immunoglobulin gene , somatic hypermutation , genetics , gene , b cell receptor , b cell , cancer research , antibody , leukemia
Abstract Associations between immunoglobulin (IG) receptors with distinctive immunogenetic features and particular gene mutations are a recurring theme in mature B‐cell lymphomas. Relevant observations have been made in chronic lymphocytic leukemia (CLL), where gene mutations are distributed asymmetrically in cases bearing or not somatic hypermutations within the clonotypic immunoglobulin heavy chain variable region (IGHV) genes (e.g. TP53 mutations predominate in IG‐unmutated CLL, whereas the opposite is seen for MYD88 mutations, enriched in IG‐mutated CLL) and in subsets of cases with stereotyped IG (enrichment for SF3B1 mutations in CLL subset #2). Moreover, similar findings have been reported in splenic marginal‐zone lymphoma, where KLF2 mutations are biased to cases expressing IGHV1‐2*04 IG receptors, and in hairy cell leukemia, where IGHV4‐34‐expressing cases display a low frequency of BRAF mutations but a high frequency of MAP2K1 mutations. The list is now growing with the report of increased frequency of inactivating mutations in the TNFAIP3 gene in MALT lymphomas expressing IG receptors encoded by the IGHV4‐34 gene, particularly of the ocular adnexa. Considering that TNFAIP3 encodes a negative regulator of NF‐κB, this finding further highlights the importance of NF‐κB pathway activation in the natural history of MALT lymphomas. Altogether, these findings allude to selection of genomic aberrations in lymphoma cases with distinctive immune signaling profiles linked to the expression of particular IG receptors. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.