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]

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

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

Rating ☆ ☆ ☆ ☆ ☆

Rating ★ ★ ★ ☆ ☆