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bibliography: 'morinlab.bib'
csl: 'NLM.csl'
link-citations: true
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[[_TOC_]]

## Overview
CD79B mutations significantly contribute to the pathogenesis of DLBCL by enhancing BCR signaling and promoting tumor survival. 
These mutations, especially when co-occurring with MYD88 mutations, define a unique molecular subtype.[@wrightProbabilisticClassificationTool2020] 
This has clinical and therapeutic implications as it may contribute sensitivity to BTK inhibitors. 
In an inducible mouse model of MYD88-driven DLBCL, CD79B mutations did not accelerate lymphomagenesis but demonstrated an increased sensitivity to pharmacological BTK inhibition.[@flumannInducibleCd79bMutation2024] 
In a retrospective analysis, younger patients with MCD DLBCL that were treated with ibrutinib had significantly better outcomes.[@wilsonEffectIbrutinibRCHOP2021]
The most common hotspot mutation in CD79B is at the tyrosine residue 196 (Y196). 
This and other common mutations primarily occur in the immunoreceptor tyrosine-based activation motif (ITAM) domain and prevent the negative regulatory feedback provided by Lyn kinase thereby enhancing BCR signaling.[@kimCD79BMYD88Mutations2014; @davisChronicActiveBcellreceptor2010]



## Relevance tier by entity

|Entity|Tier|Description                           |
|:------:|:----:|--------------------------------------|
|![DLBCL](images/icons/DLBCL_tier1.png) |1   |high-confidence DLBCL gene with functional evidence[@davisChronicActiveBcellreceptor2010;@morinFrequentMutationHistonemodifying2011]|
|![FL](images/icons/FL_tier2.png)    |2   |relevance in FL not firmly established|
|![BL](images/icons/BL_tier2.png)    |3   |Retired, Failed QC[@paneaWholeGenomeLandscape2019]|

## Mutation incidence in large patient cohorts (GAMBL reanalysis)

[[include:DLBCL_CD79B.md]]
[[include:FL_CD79B.md]]

## Mutation pattern and selective pressure estimates

[[include:dnds_CD79B.md]]

## CD79B Hotspots

Mutations at Y196 enhance B-cell receptor (BCR) signaling by preventing the negative regulatory feedback provided by Lyn kinase, a feedback inhibitor of BCR signaling. This results in continuous activation of the NF-κB pathway, promoting tumor cell survival and proliferation.[@kimCD79BMYD88Mutations2014]

| Chromosome |Coordinate (hg19) | ref>alt | HGVSp | 
 | :---:| :---: | :--: | :---: |
| chr17 | 62007234 | C>G | A150P |
| chr17 | 62007234 | C>T | A150T |
| chr17 | 62007233 | G>A | A150V |
| chr17 | 62007140 | A>G | L181P |
| chr17 | 62007129 | C>T | X184_splice |
| chr17 | 62006798 | T>A | Y197F |
| chr17 | 62006798 | T>C | Y197C |
| chr17 | 62006799 | A>C | Y197D |
| chr17 | 62006799 | A>G | Y197H |
| chr17 | 62006798 | T>G | Y197S |
| chr17 | 62006795 | T>C | E198G |
| chr17 | 62006680 | A>G | L200P |
| chr17 | 62006680 | A>C | L200R |
| chr17 | 62006680 | A>T | L200Q |
| chr17 | 62006603 | G>A | H226Y |
| chr17 | 62006603 | G>T | H226N |

[[include:browser_CD79B.md]]

## Expression
![](images/gene_expression/CD79B_by_pathology.svg)

## Representative Mutations

### BL

![](primary/Panea_CD79B.svg)
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![](primary/Panea_CD79B_2.svg)
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[[include:mermaid_CD79B.md]]

## References
<!-- ORIGIN: morinFrequentMutationHistonemodifying2011 -->
<!-- DLBCL: morinFrequentMutationHistonemodifying2011 -->
<!-- BL: paneaWholeGenomeLandscape2019 -->