--- bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true --- [[_TOC_]] ## 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](https://github.com/morinlab/LLMPP/wiki/ashm) 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](images/icons/PMBL_tier1.png)|1|high-confidence PMBL/cHL/GZL gene[@mottokIntegrativeGenomicAnalysis2019]| |![BL](images/icons/BL_tier2.png) |2 | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@paneaWholeGenomeLandscape2019]| |![DLBCL](images/icons/DLBCL_tier1.png) |1 | aSHM target and high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011]| |![FL](images/icons/FL_tier1.png) |1 | aSHM target and high-confidence FL gene [@morinFrequentMutationHistonemodifying2011]| ## Mutation incidence in large patient cohorts (GAMBL reanalysis) [[include:DLBCL_IRF8.md]] [[include:FL_IRF8.md]] [[include:BL_IRF8.md]] ## Mutation pattern and selective pressure estimates [[include:dnds_IRF8.md]] ## aSHM regions |chr_name|hg19_start|hg19_end|region |regulatory_comment| |:--------:|:----------:|:--------:|:------------------------------------------------------------------------------------------:|:------------------:| |chr16 |85931918 |85933977|[TSS](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr16%3A85931918%2D85933977)|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:browser_IRF8.md]] ## Expression ![](images/gene_expression/IRF8_by_pathology.svg) [[include:mermaid_IRF8.md]] ## References [@wrightProbabilisticClassificationTool2020] [@qiuIRF8mutantCellLymphoma2024]