Table of Contents

Overview

IRF8 (Interferon Regulatory Factor 8) is a transcription factor critical for the development and function of B lymphocytes. Mutations in IRF8 have been implicated in various lymphoid malignancies, most predominantly in FL and DLBCL. IRF8 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. Coding and non-coding mutations in IRF8 are associated with the EZB subgroup of DLBCL. There is preliminary evidence that IRF8 mutations contribute to immune evasion by downregulating CD74 and HLA-DM in DLBCL. These are crucial for processing and presentation of self antigens.

Relevance tier by entity

Entity Tier Description
PMBL 1 high-confidence PMBL/cHL/GZL gene1
BL 2 aSHM target; Although recurrent, the relevance of mutations in BL is tenuous2
DLBCL 1 aSHM target and high-confidence DLBCL gene3
FL 1 aSHM target and high-confidence FL gene3

Mutation incidence in large patient cohorts (GAMBL reanalysis)

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Mutation pattern and selective pressure estimates

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aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr16 85931918 85933977 TSS active_promoter

IRF8 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr16 85936688 T>C Y23H
chr16 85936701 T>G I27S
chr16 85936784 T>G S55A
chr16 85936788 T>C I56T
chr16 85942602 G>T A61S
chr16 85942618 A>G K66R
chr16 85942671 T>C C84R
chr16 85942692 G>A D91N

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Expression

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References

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