CD70

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
CD70 Hotspots
Expression
History
References

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.¹ CD70 mutations are associated with the BN2 genetic subtype of DLBCL.² 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.¹ In mouse models, CD70 loss promoted lymphomagenesis, consistent with its role as a tumor suppressor gene in B-cell lymphomas.³

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).¹

Relevance tier by entity

Entity	Tier	Description
	1	High-confidence DLBCL gene
	2	Role of CD70 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	87	0.0799	[0.0638,0.096]
DLBCL	GAMBL with Reddy	2,088	156	0.0747	[0.0634,0.086]
DLBCL	BC	231	9	0.0390	[0.014,0.0639]
DLBCL	Dana-Farber	303	24	0.0792	[0.0488,0.1096]
DLBCL	NCI	470	44	0.0936	[0.0673,0.12]
DLBCL	Reddy	999	69	0.0691	[0.0533,0.0848]
DLBCL	DLBCL_ICGC	85	10	0.1176	[0.0492,0.1861]

FL

pathology	Collection	N	mutated	Incidence	CI
FL	GAMBL without Crouch	642	5	0.0078	[0.001,0.0146]
FL	GAMBL with Crouch	1,189	13	0.0109	[0.005,0.0168]
FL	BC	379	2	0.0053	[0,0.0126]
FL	Kalmbach	164	1	0.0061	[0,0.018]
FL	Crouch	547	8	0.0146	[0.0046,0.0247]
FL	FL_ICGC	99	2	0.0202	[0,0.0479]

Mutation pattern and selective pressure estimates

Entity	Missense dN/dS	Nonsense dN/dS	Q value
BL	1.9262	0.0000	1
FL	2.1212	68.8921	1
DLBCL	3.3831	35.2429	0

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

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Expression

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

References

Nie M, Ren W, Ye X, Berglund M, Wang X, Fjordén K, Du L, Giannoula Y, Lei D, Su W, Li W, Liu D, Linderoth J, Jiang C, Bao H, Jiang W, Huang H, Hou Y, Zhu S, Enblad G, Jerkeman M, Wu K, Zhang H, Amini RM, Li ZM, Pan-Hammarström Q. The dual role of CD70 in B-cell lymphomagenesis. Clin Transl Med. 2022 Dec;12(12):e1118. PMCID: PMC9722974

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

Russler-Germain DA, Krysiak K, Ramirez CA, Mosior M, Watkins MP, Gomez F, Skidmore ZL, Trani L, Gao F, Geyer S, Cashen A, Mehta-Shah N, Kahl B, Bartlett N, Alderuccio J, Lossos I, Ondrejka S, Hsi E, Martin P, Leonard J, Griffith M, Griffith O, Fehniger T. Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303. Blood Advances. 2023;7:5524–5539.