CD79B

Table of Contents

Overview
Experimental Evidence
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
- DLBCL
- FL
Mutation pattern and selective pressure estimates
CD79B Hotspots
Expression
Representative Mutations
- BL
History
References

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.¹ 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.² In a retrospective analysis, younger patients with MCD DLBCL that were treated with ibrutinib had significantly better outcomes.³ 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.^4,5

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a gain of function (GOF).⁵

Relevance tier by entity

Entity	Tier	Description
	3	Mutations are unlikely to be relevant to BL
	1	High-confidence DLBCL gene
	2	Role of CD79B mutations in FL requires confirmation

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity	Collection	N	mutated	Incidence	95% CI
DLBCL	GAMBL without Reddy	1,089	143	0.1313	[0.1113,0.1514]
DLBCL	GAMBL with Reddy	2,088	226	0.1082	[0.0949,0.1216]
DLBCL	BC	231	21	0.0909	[0.0538,0.128]
DLBCL	Dana-Farber	303	44	0.1452	[0.1055,0.1849]
DLBCL	NCI	470	70	0.1489	[0.1167,0.1811]
DLBCL	Reddy	999	83	0.0831	[0.066,0.1002]
DLBCL	DLBCL_ICGC	85	8	0.0941	[0.032,0.1562]

FL

pathology	Collection	N	mutated	Incidence	CI
FL	GAMBL without Crouch	642	14	0.0218	[0.0105,0.0331]
FL	GAMBL with Crouch	1,189	33	0.0278	[0.0184,0.0371]
FL	BC	379	7	0.0185	[0.0049,0.032]
FL	Kalmbach	164	3	0.0183	[0,0.0388]
FL	Crouch	547	19	0.0347	[0.0194,0.0501]
FL	FL_ICGC	99	4	0.0404	[0.0016,0.0792]

Mutation pattern and selective pressure estimates

Entity	Missense dN/dS	Nonsense dN/dS	Q value
BL	4.0629	0.0000	1
FL	1.7998	12.4220	0
DLBCL	2.6876	5.5426	0

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.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

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Expression

Representative Mutations

BL

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History

%%{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

References

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Flümann R, Hansen J, Meinel J, Pfeiffer P, Goldfarb Wittkopf H, Lütz A, Wirtz J, Möllmann M, Zhou T, Tabatabai A, Lohmann T, Jauch M, Beleggia F, Pelzer B, Ullrich F, Höfmann S, Arora A, Persigehl T, Büttner R, von Tresckow B, Klein S, Jachimowicz RD, Reinhardt HC, Knittel G. An inducible Cd79b mutation confers ibrutinib sensitivity in mouse models of Myd88-driven diffuse large B-cell lymphoma. Blood Adv. 2024 Mar 12;8(5):1063–1074. PMCID: PMC10907402

Wilson WH, Wright GW, Huang DW, Hodkinson B, Balasubramanian S, Fan Y, Vermeulen J, Shreeve M, Staudt LM. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL. Cancer Cell. 2021 Dec 13;39(12):1643–1653.e3. PMCID: PMC8722194

Kim Y, Ju H, Kim DH, Yoo HY, Kim SJ, Kim WS, Ko YH. CD79B and MYD88 mutations in diffuse large B-cell lymphoma. Hum Pathol. 2014 Mar;45(3):556–564.

Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, Xu W, Shaffer AL, Wright G, Xiao W, Powell J, Jiang JK, Thomas CJ, Rosenwald A, Ott G, Müller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010 Jan;463(7277):88–92. PMCID: PMC2845535

Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJM, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298–303. PMCID: PMC3210554

Panea R, Love C, Shingleton JR, Reddy A, Bailey J, Moormann A, Otieno J, Ong’echa J, Oduor C, Schroêder K, Masalu N, Chao N, Agajanian M, Major M, Fedoriw Y, Richards K, Rymkiewicz G, Miles R, Alobeid B, Bhagat G, Flowers C, Ondrejka S, Hsi E, Choi W, Au-Yeung R, Hartmann W, Lenz G, Meyerson H, Lin YY, Zhuang Y, Luftig M, Waldrop A, Dave T, Thakkar D, Sahay H, Li G, Palus B, Seshadri V, Kim S, Gascoyne R, Levy S, Mukhopadhyay M, Dunson D, Dave S. The whole genome landscape of Burkitt lymphoma subtypes. Blood. 2019;