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.

Experimental Evidence

Driver mutations affecting this gene in DLBCL/FL have been experimentally demonstrated to cause a reduction or loss of function (LOF).1

Relevance tier by entity

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 104 0.0955 [0.078,0.113]
DLBCL GAMBL with Reddy 2,088 180 0.0862 [0.0742,0.0982]
DLBCL BC 231 22 0.0952 [0.0574,0.1331]
DLBCL Dana-Farber 303 29 0.0957 [0.0626,0.1288]
DLBCL NCI 470 49 0.1043 [0.0766,0.1319]
DLBCL Reddy 999 76 0.0761 [0.0596,0.0925]
DLBCL DLBCL_ICGC 85 4 0.0471 [0.002,0.0921]
pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 73 0.1137 [0.0892,0.1383]
FL GAMBL with Crouch 1,189 158 0.1329 [0.1136,0.1522]
FL BC 379 41 0.1082 [0.0769,0.1395]
FL Kalmbach 164 22 0.1341 [0.082,0.1863]
FL Crouch 547 85 0.1554 [0.125,0.1858]
FL FL_ICGC 99 10 0.1010 [0.0416,0.1604]
pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 2 0.0030 [0,0.009]
BL GAMBL without ICGC/Zhou 320 9 0.0128 [6e-04,0.025]
BL GAMBL with Panea 410 9 0.0039 [0,0.0099]
BL BLGSP 219 2 0.0091 [0,0.0217]
BL Zhou/ICGC 90 0 0.0011 [0,0.008]
BL Panea 101 7 0.0693 [0.0198,0.1188]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 0.9184 0.0000 1
FL 6.6672 36.4648 0
DLBCL 4.2190 7.1453 0

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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Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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