CD79B - morinlab/LLMPP GitHub Wiki

bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @flumannInducibleCd79bMutation2024, @wrightProbabilisticClassificationTool2020, @morinFrequentMutationHistonemodifying2011, @davisChronicActiveBcellreceptor2010, @wilsonEffectIbrutinibRCHOP2021, @kimCD79BMYD88Mutations2014, @paneaWholeGenomeLandscape2019,

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]

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a gain of function (GOF).[@davisChronicActiveBcellreceptor2010]

Relevance tier by entity

include:tables/table1_CD79B.md

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

include:tables/DLBCL_CD79B.md

FL

include:tables/FL_CD79B.md

Mutation pattern and selective pressure estimates

include:tables/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