refine overview

+These mutations are caused by the somatic hypermutation process. The presence of these mutations are strongly correlated with the presence of a translocation between BCL2 and one of the immunoglobulin loci.

+[Selective pressure analysis](#mutation-pattern-and-selective-pressure-estimates) did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers. Although mutations may not be under positive selective pressure in the context of lymphomagenesis, some of these mutations may interfere with the function of BCL2 antagonists.

+Although common, particularly in DLBCL, the function of many of these mutations remains unclear but some have been shown to affect the regulation of BCL6 expression. The role of BCL6 missense mutations remains unclear.

+CIITA encodes the major histocompatibility complex (MHC) class II transactivator. CIITA mutations are frequent in PMBCL. These mutations often include structural genomic rearrangements, missense, nonsense, and frameshift mutations. In PMBCL, these mutations are thought to contribute to loss of MHC expression.[@mottokGenomicAlterationsCIITA2015] Although loss of CIITA and MHC Class II Expression is commonly observed in DLBCL, the role of mutations and methylation affecting this locus remains unclear.[@morinFrequentMutationHistonemodifying2011] CIITA 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. The relevance of CIITA mutations in DLBCL remains unclear. [Selective pressure analysis](#mutation-pattern-and-selective-pressure-estimates) did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers.

+### BL

+[[include:tables/BL_ETS1.md]]

+

+This gene encodes the H2A protein, one of the core proteins comprising nucleosomes. Although relatively common in DLBCL, little is known about the function of these mutations. The relevance of HIST1H2AM mutations in DLBCL remains unclear. [Selective pressure analysis](#mutation-pattern-and-selective-pressure-estimates) did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers.

+This gene encodes the H2A protein, one of the core proteins comprising nucleosomes. Although relatively common in DLBCL, little is known about the function of these mutations. The relevance of HIST1H2AC mutations in DLBCL remains unclear.

+[Selective pressure analysis](#mutation-pattern-and-selective-pressure-estimates) did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers.

+## Overview

+

+The relevance of HIST1H3B mutations in DLBCL remains unclear.

+[Selective pressure analysis](#mutation-pattern-and-selective-pressure-estimates) did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers.

+## Overview

+

+Although IGLL5 is significantly mutated, [Selective pressure analysis](#mutation-pattern-and-selective-pressure-estimates) implies the gene is largely under negative selective pressure. It remains unclear whether any of the mutations in IGLL5 are relevant to DLBCL, BL or FL.

+IRF4 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. Although IRF4 is significantly mutated in DLBCL, [Selective pressure analysis](#mutation-pattern-and-selective-pressure-estimates) implies the gene is largely under negative selective pressure.

+There are a few mutation hotspots in IRF4. It remains unclear whether any of the mutations in IRF4 are relevant to lymphomagenesis.

+ @morinFrequentMutationHistonemodifying2011, @mottokIntegrativeGenomicAnalysis2019, @qiuIRF8mutantCellLymphoma2024, @wrightProbabilisticClassificationTool2020, @paneaWholeGenomeLandscape2019, @qiuIRF8mutantCellLymphoma2024

+There is preliminary evidence that IRF8 mutations contribute to immune evasion by downregulating CD74 and HLA-DM in DLBCL.[@qiuIRF8mutantCellLymphoma2024]