FBXW7

Table of Contents

Overview
Experimental Evidence
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
Mutation pattern and selective pressure estimates
Expression
References

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)

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Mutation pattern and selective pressure estimates

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Expression

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References

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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

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

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

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

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