CD70

Overview

CD70 is a costimulatory molecule expressed on some activated lymphocytes and has a role in T-cell-mediated immune responses. CD70 aberrations are relatively common in DLBCL and appear more frequent in certain DLBCL patient populations. For instance, in a Chinese DLBCL cohort, 24% of cases exhibited CD70 genetic changes, compared to 10.8% in a Swedish cohort.^{nieDualRoleCD702022b?} CD70 mutations are associated with the BN2 genetic subtype of DLBCL.¹ The mutation pattern in CD70 is consistent with the preferential accumulation of inactivating mutations. Genetic perturbation limits the development of an effective CD8+ T-cell immune response in Bcl6-driven DLBCL.^{nieDualRoleCD702022b?} In mouse models, CD70 loss promoted lymphomagenesis, consistent with its role as a tumor suppressor gene in B-cell lymphomas.²

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-27 : Morin : DLBCL 2012-03-06 : Lohr : 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 2023-07-26 : Russler-Germain : FL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence DLBCL gene³
	2	relevance in FL not firmly established^{russler-germainMutationsAssociatedProgression2023b?}

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	5.54
DLBCL	Schmitz cohort	9.36
DLBCL	Reddy cohort	6.91
DLBCL	Chapuy cohort	7.69
FL	GAMBL genomes	1.15
BL	GAMBL genomes+capture	0.92
BL	Thomas cohort	0.40
BL	Panea cohort	3.00

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	No	2.199	0.000
DLBCL	No	Yes	28.493	249.836
FL	No	No	0.000	106.251

CD70 Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr19	6590145	C>T	W55*
chr19	6590138	C>T	A58T
chr19	6590138	C>G	A58P
chr19	6590137	G>A	A58V
chr19	6590116	G>A	T65I

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

CD70 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.

Mandato E, Calabretta E, Bai G, Song L, Sun Y, Shanmugam V, Paczkowska J, Choi IK, Redd R, Tang M, Lawton LN, Neuberg D, Rodig S, Michor F, Zhang B, Shipp MA. Abstract A38: Cd70 genetic perturbation limits the development of an effective CD8+ T-cell immune response to Bcl6-driven diffuse large B-cell lymphoma. Blood Cancer Discovery. 2022 Sep 6;3:A38.

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