EBF1

Overview

EBF1 is a critical transcription factor in early B-cell development, regulating the expression of key genes involved in B-cell differentiation, survival, and function. EBF1 is essential for proper B-cell receptor (BCR) signaling.¹ Mutations in EBF1 can impair BCR signaling pathways, affecting B-cell survival and proliferation.¹ EBF1 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. This gene has some recurrent sites of mutations (hot spots) but the mutation pattern in DLBCL and FL implies the preferential accumulation of inactivating mutations.

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012-10-01 : Bohle : DLBCL 2013-08-15 : Morin : DLBCL 2015-02-12 : Reichel : PMBL 2017-05-01 : Albuquerque : DLBCL 2017-10-10 : Reddy : DLBCL 2018-05-01 : Chapuy : DLBCL 2018-10-01 : Arthur : DLBCL 2021-05-05 : Hubschmann : DLBCL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene^{reichelFlowSortingExome2015a?}
	1-a	aSHM target and high-confidence DLBCL gene^{1,2,albuquerqueEnhancingKnowledgeDiscovery2017a?}
	1-a	aSHM target and high-confidence FL gene
	2-a	aSHM target; Although recurrent, the relevance of mutations in BL is tenuous³

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	2.08
BL	Thomas cohort	1.30
BL	Panea cohort	5.90
DLBCL	GAMBL genomes	8.99
DLBCL	Schmitz cohort	10.85
DLBCL	Reddy cohort	8.81
DLBCL	Chapuy cohort	12.82
FL	GAMBL genomes	8.55

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	2.304	0.000
DLBCL	Yes	Yes	11.910	66.114
FL	Yes	Yes	17.826	91.742

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr5	158500476	158532769	TSS	active_promoter

EBF1 Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr5	158526467	C>T	S7N
chr5	158526456	T>C	S11G
chr5	158526413	T>C	N25S
chr5	158511720	T>C	N147D
chr5	158511714	C>T	E149K
chr5	158511705	G>C	R152G
chr5	158511698	A>C	L154W
chr5	158511677	C>A	C161F
chr5	158500470	C>T	R163H
chr5	158500468	A>G	C164R
chr5	158500467	C>G	C164S

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

EBF1 Expression

References

*Györy I, Boller S, Nechanitzky R, Mandel E, Pott S, Liu E, Grosschedl R. Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells. Genes Dev. 2012 Apr 1;26(7):668-82. doi: 10.1101/gad.18$

Bohle V, Döring C, Hansmann M-L, Küppers R. Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma. Leukemia. 2013 Mar;27(3):671–679.

Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992

Thomas N, Dreval K, Gerhard DS, Hilton LK, Abramson JS, Ambinder RF, Barta S, Bartlett NL, Bethony J, Bhatia K, Bowen J, Bryan AC, Cesarman E, Casper C, Chadburn A, Cruz M, Dittmer DP, Dyer MA, Farinha P, Gastier-Foster JM, Gerrie AS, Grande BM, Greiner T, Griner NB, Gross TG, Harris NL, Irvin JD, Jaffe ES, Henry D, Huppi R, Leal FE, Lee MS, Martin JP, Martin MR, Mbulaiteye SM, Mitsuyasu R, Morris V, Mullighan CG, Mungall AJ, Mungall K, Mutyaba I, Nokta M, Namirembe C, Noy A, Ogwang MD, Omoding A, Orem J, Ott G, Petrello H, Pittaluga S, Phelan JD, Ramos JC, Ratner L, Reynolds SJ, Rubinstein PG, Sissolak G, Slack G, Soudi S, Swerdlow SH, Traverse-Glehen A, Wilson WH, Wong J, Yarchoan R, ZenKlusen JC, Marra MA, Staudt LM, Scott DW, Morin RD. Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma. Blood. 2023 Feb 23;141(8):904–916. PMCID: PMC10023728