IRF8 - morinlab/LLMPP GitHub Wiki

bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @morinFrequentMutationHistonemodifying2011, @mottokIntegrativeGenomicAnalysis2019, @qiuIRF8mutantCellLymphoma2024, @wrightProbabilisticClassificationTool2020, @paneaWholeGenomeLandscape2019, @qiuIRF8mutantCellLymphoma2024

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.[@qiuIRF8mutantCellLymphoma2024] 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).[@qiuIRF8mutantCellLymphoma2024]

Relevance tier by entity

include:tables/table1_IRF8.md

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Mutation pattern and selective pressure estimates

include:tables/dnds_IRF8.md

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

include:tables/browser_IRF8.md

Expression

include:tables/mermaid_IRF8.md

References

[@wrightProbabilisticClassificationTool2020] [@qiuIRF8mutantCellLymphoma2024]