Table of Contents

Overview

IRF4 (Interferon Regulatory Factor 4) encodes a transcription factor that plays a critical role in the regulation of immune response genes and B-cell development. Mutations and rearrangements in the IRF4 gene have been implicated in various B-cell lymphomas, including DLBCL. IRF4-rearranged large B-cell lymphomas (LBCL-IRF4) show a unique molecular profile with strong expression of IRF4/MUM1 and are associated with favorable outcomes. MUM1 staining is also commonly used to assign DLBCLs to one of the two cell-of-origin (COO) subgroups by immunohistochemistry. IRF4 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. There are a few mutation hotspots in this gene. The functional role of mutations in IRF4 in the absence of a rearrangement remains poorly understood.

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 48 0.0441 [0.0319,0.0563]
DLBCL GAMBL with Reddy 2,088 92 0.0441 [0.0353,0.0529]
DLBCL BC 231 4 0.0173 [5e-04,0.0341]
DLBCL Dana-Farber 303 6 0.0198 [0.0041,0.0355]
DLBCL NCI 470 33 0.0702 [0.0471,0.0933]
DLBCL Reddy 999 44 0.0440 [0.0313,0.0568]
DLBCL DLBCL_ICGC 85 5 0.0588 [0.0088,0.1088]
pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 6 0.0093 [0.0019,0.0168]
FL GAMBL with Crouch 1,189 9 0.0076 [0.0026,0.0125]
FL BC 379 5 0.0132 [0.0017,0.0247]
FL Kalmbach 164 1 0.0061 [0,0.018]
FL Crouch 547 3 0.0055 [0,0.0117]
FL FL_ICGC 99 0 0.0010 [0,0.0073]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 0.5756 0.0000 1.0000
FL 4.0661 0.0000 1.0000
DLBCL 1.5057 0.5137 0.0187

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr6 390572 394093 TSS active_promoter

IRF4 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr6 393328 A>G K59R
chr6 393340 A>G N63S
chr6 393360 C>G L70V
chr6 393360 C>T L70F

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Expression

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References

1.
Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJM, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298–303. PMCID: PMC3210554
2.
Mottok A, Hung SS, Chavez EA, Woolcock B, Telenius A, Chong LC, Meissner B, Nakamura H, Rushton C, Viganò E, Sarkozy C, Gascoyne RD, Connors JM, Ben-Neriah S, Mungall A, Marra MA, Siebert R, Scott DW, Savage KJ, Steidl C. Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma. Blood. 2019 Sep 5;134(10):802–813.

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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