CD79B
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.[@wilsonEffectIbrutinibRCHOP2021b] 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]
%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%%
timeline
title Publication timing
2011-07-27 : Morin : DLBCL
2012-03-06 : Lohr : DLBCL
2013-01-01 : Zhang : DLBCL
2013-08-15 : Morin : DLBCL
2017-05-01 : Albuquerque : DLBCL
2017-10-10 : Reddy : DLBCL
2018-04-12 : Schmitz : DLBCL
2018-05-01 : Chapuy : DLBCL
2018-10-01 : Arthur : DLBCL
2019-09-26 : Panea : BL
| Entity | Tier | Description |
|---|---|---|
 |
1-EE | high-confidence DLBCL gene with functional evidence[@davisChronicActiveBcellreceptor2010] [@morinFrequentMutationHistonemodifying2011] |
 |
2 | relevance in FL not firmly established |
 |
3 | Retired, Failed QC[@paneaWholeGenomeLandscape2019] |
| Entity | source | frequency (%) |
|---|---|---|
| BL | GAMBL genomes+capture | 1.39 |
| BL | Thomas cohort | 0.00 |
| BL | Panea cohort | 4.00 |
| DLBCL | GAMBL genomes | 9.94 |
| DLBCL | Schmitz cohort | 14.89 |
| DLBCL | Reddy cohort | 8.31 |
| DLBCL | Chapuy cohort | 15.38 |
| FL | GAMBL genomes | 2.77 |
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | No | No | 0.000 | 0.000 |
| DLBCL | No | Yes | 16.616 | 41.932 |
| FL | No | No | 10.310 | 0.000 |
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.4
| 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 |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
Rating
☆ ☆ ☆ ☆ ☆
Rating
★ ★ ★ ☆ ☆
Disclaimer
The content in these pages has been populated, in part, by an automated process. Although we have scrutinized every page to ensure accuracy, errors will inevitably exist. If you find an error please report it as an issue and we will address it.
In particular, let us know if you feel that an important citation is missing or if a paper has been cited incorrectly.
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
Share — copy and redistribute the material in any medium or format for any purpose, even commercially.
Adapt — remix, transform, and build upon the material for any purpose, even commercially. The licensor cannot revoke these freedoms as long as you follow the license terms.