CD79B - morinlab/LLMPP GitHub Wiki
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]
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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 |
---|---|---|
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1-EE | high-confidence DLBCL gene with functional evidence[@davisChronicActiveBcellreceptor2010] [@morinFrequentMutationHistonemodifying2011] |
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2 | relevance in FL not firmly established |
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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-ÎșB 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
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