CXCR4

Overview

CXCR4 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. No notable hot spots have been described in this gene in the context of the cancers listed below. The mutation pattern in DLBCL implies the preferential accumulation of inactivating mutations.

History

Mutations in this gene were first described in DLBCL in 2012 by Khodabakhshi et al,¹ in FL in 2021 by Hübschmann et al² and in BL in 2019 by Panea et al.³

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012-11-12 : Khodabakhshi : DLBCL 2017-01-26 : Krysiak : FL 2019-09-26 : Panea : BL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence MZL gene
	1-a	aSHM target and high-confidence DLBCL gene
	2-a	aSHM target; Although recurrent, the relevance of mutations in FL is tenuous
	2-a	aSHM target; Although recurrent, the relevance of mutations in BL is tenuous

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	2.08
BL	Thomas cohort	2.10
BL	Panea cohort	2.00
DLBCL	GAMBL genomes	2.87
DLBCL	Schmitz cohort	2.55
DLBCL	Reddy cohort	1.50
DLBCL	Chapuy cohort	2.56
FL	GAMBL genomes	3.46

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	4.603	0.000
DLBCL	Yes	No	3.731	18.727
FL	Yes	No	0.000	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr2	136874728	136875461	intron	weak_promoter

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

CXCR4 Expression

Representative Mutations

BL

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References

Khodabakhshi AH, Morin RD, Fejes AP, Mungall AJ, Mungall KL, Bolger-Munro M, Johnson NA, Connors JM, Gascoyne RD, Marra MA, Birol I, Jones SJM. Recurrent targets of aberrant somatic hypermutation in lymphoma. Oncotarget. 2012 Nov 12;3(11):1308–1319. PMCID: PMC3717795
Hübschmann D, Kleinheinz K, Wagener R, Bernhart SH, López C, Toprak UH, Sungalee S, Ishaque N, Kretzmer H, Kreuz M, Waszak SM, Paramasivam N, Ammerpohl O, Aukema SM, Beekman R, Bergmann AK, Bieg M, Binder H, Borkhardt A, Borst C, Brors B, Bruns P, Carrillo de Santa Pau E, Claviez A, Doose G, Haake A, Karsch D, Haas S, Hansmann ML, Hoell JI, Hovestadt V, Huang B, Hummel M, Jäger-Schmidt C, Kerssemakers JNA, Korbel JO, Kube D, Lawerenz C, Lenze D, Martens JHA, Ott G, Radlwimmer B, Reisinger E, Richter J, Rico D, Rosenstiel P, Rosenwald A, Schillhabel M, Stilgenbauer S, Stadler PF, Martín-Subero JI, Szczepanowski M, Warsow G, Weniger MA, Zapatka M, Valencia A, Stunnenberg HG, Lichter P, Möller P, Loeffler M, Eils R, Klapper W, Hoffmann S, Trümper L, ICGC MMML-Seq consortium, ICGC DE-Mining consortium, BLUEPRINT consortium, Küppers R, Schlesner M, Siebert R. Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas. Leukemia. 2021 Jul;35(7):2002–2016. PMCID: PMC8257491
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;