Table of Contents

Overview

FBXW7 mutations are found in a range of lymphoid malignancies, including B-cell lymphomas. These mutations often include missense mutations, deletions, frameshift mutations and splice-site mutations. Overall, these mutations are relatively rare in DLBCL and occur more frequently in other solid tumors as well as T-cell acute lymphocytic leukemia.1 The most commonly observed mutations in those cancers are the hot spots R465 and R479.1 In leukemias, FBXW7 mutations enhance the activity of leukemia-initiating cells by stabilizing oncogenic MYC.2 Whether they have this role in DLBCL remains to be determined.

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).3

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 29 0.0266 [0.0171,0.0362]
DLBCL GAMBL with Reddy 2,088 42 0.0201 [0.0141,0.0261]
DLBCL BC 231 7 0.0303 [0.0082,0.0524]
DLBCL Dana-Farber 303 7 0.0231 [0.0062,0.04]
DLBCL NCI 470 14 0.0298 [0.0144,0.0452]
DLBCL Reddy 999 13 0.0130 [0.006,0.02]
DLBCL DLBCL_ICGC 85 1 0.0118 [0,0.0347]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 5.3375 8.7890 1.0000
FL 6.8799 6.6518 1.0000
DLBCL 2.6714 4.5617 0.0508

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Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2013-01-01 : Zhang : DLBCL 2017-10-10 : Reddy : DLBCL 2021-05-05 : Hubschmann : DLBCL

References

1.
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King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P, Aranda-Orgilles B, Perez-Garcia A, Shi J, Vakoc C, Sandy P, Shen SS, Ferrando A, Aifantis I. The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell. 2013 Jun;153(7):1552–1566. PMCID: PMC4146439
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Saffie R, Zhou N, Rolland D, Önder Ö, Basrur V, Campbell S, Wellen KE, Elenitoba-Johnson KSJ, Capell BC, Busino L. FBXW7 Triggers Degradation of KMT2D to Favor Growth of Diffuse Large B-cell Lymphoma Cells. Cancer Res. 2020 Jun 15;80(12):2498–2511. PMCID: PMC7417195
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Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, Leppa S, Pasanen A, Meriranta L, Karjalainen-Lindsberg ML, Nørgaard P, Pedersen M, Gang AO, Høgdall E, Heavican TB, Lone W, Iqbal J, Qin Q, Li G, Kim SY, Healy J, Richards KL, Fedoriw Y, Bernal-Mizrachi L, Koff JL, Staton AD, Flowers CR, Paltiel O, Goldschmidt N, Calaminici M, Clear A, Gribben J, Nguyen E, Czader MB, Ondrejka SL, Collie A, Hsi ED, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Choi WWL, Evens AM, Pilichowska M, Sengar M, Reddy N, Li S, Chadburn A, Gordon LI, Jaffe ES, Levy S, Rempel R, Tzeng T, Happ LE, Dave T, Rajagopalan D, Datta J, Dunson DB, Dave SS. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell. 2017 Oct;171(2):481–494.e15. PMCID: PMC5659841
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Zhang J, Grubor V, Love CL, Banerjee A, Richards KL, Mieczkowski PA, Dunphy C, Choi W, Au WY, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers C, Naresh K, Evens A, Gordon LI, Czader M, Gill JI, Hsi ED, Liu Q, Fan A, Walsh K, Jima D, Smith LL, Johnson AJ, Byrd JC, Luftig MA, Ni T, Zhu J, Chadburn A, Levy S, Dunson D, Dave SS. Genetic heterogeneity of diffuse large B-cell lymphoma. Proceedings of the National Academy of Sciences of the United States of America. 2013;110:1398–1403. PMCID: PMC3557051

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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