Table of Contents

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

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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

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References

1.
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
2.
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.
3.
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.
4.
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
5.
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.

Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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