CD79B

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.^{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.

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-27 : Morin : DLBCL 2019-09-26 : Panea : BL

Relevance tier by entity

Entity	Tier	Description
	2	relevance in BL not firmly established³
	1	high-confidence DLBCL gene⁴
	2	relevance in FL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

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

Mutation pattern and selective pressure estimates

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

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

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

CD79B Expression

References

Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A, Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW, Staudt LM. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 Apr 13;37(4):551-568.e14. doi: 10.1016/j.ccell.2020.03.015. PMID: 32289277; PMCID: PMC8459709.
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. doi: 10.1182/bloodadvances.2023011213. PMID: 38060829; 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. doi: 10.1016/j.ccell.2021.10.006. Epub 2021 Nov 4. PMID: 34739844; 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):556-64. doi: 10.1016/j.humpath.2013.10.023. Epub 2013 Oct 31. PMID: 24444466.

Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A, Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW, Staudt LM. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 Apr 13;37(4):551–568.e14.

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

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;

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