FAS

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
Expression
References

Overview

FAS encodes a cell surface receptor involved in the induction of apoptosis. FAS mutations are common in DLBCL and may be more frequent in primary gastric DLBCL.¹,² Mutations also occur in FL at a lower rate.³ Although reported in one BL study,⁴ overall the evidence for FAS mutations in BL remains sparse. Mutations in FAS often lead to a loss of function, making lymphoma cells resistant to Fas ligand-induced apoptosis, thereby allowing malignant cells to evade immune surveillance.⁵ In mouse models, Fas mutations led to a significantly shorter lymphoma-specific survival and reduced sensitivity to chemotherapy.⁵

Experimental Evidence

Driver mutations affecting this gene in FL/DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).⁶

Relevance tier by entity

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

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FL

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Mutation pattern and selective pressure estimates

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Expression

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References

Wohlfart S, Sebinger D, Gruber P, Buch J, Polgar D, Krupitza G, Rosner M, Hengstschläger M, Raderer M, Chott A, Müllauer L. FAS (CD95) mutations are rare in gastric MALT lymphoma but occur more frequently in primary gastric diffuse large B-cell lymphoma. The American Journal of Pathology. 2004 Mar;164(3):1081–1089. PMCID: PMC1614721

Scholl V, Stefanoff CG, Hassan R, Spector N, Renault IZ. Mutations within the 5’ region of FAS/CD95 gene in nodal diffuse large B-cell lymphoma. Leuk Lymphoma. 2007 May;48(5):957–963.

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

Panea R, Love C, Shingleton JR, Reddy A, Bailey J, Moormann A, Otieno J, Ong’echa J, Oduor C, Schroêder K, Masalu N, Chao N, Agajanian M, Major M, Fedoriw Y, Richards K, Rymkiewicz G, Miles R, Alobeid B, Bhagat G, Flowers C, Ondrejka S, Hsi E, Choi W, Au-Yeung R, Hartmann W, Lenz G, Meyerson H, Lin YY, Zhuang Y, Luftig M, Waldrop A, Dave T, Thakkar D, Sahay H, Li G, Palus B, Seshadri V, Kim S, Gascoyne R, Levy S, Mukhopadhyay M, Dunson D, Dave S. The whole genome landscape of Burkitt lymphoma subtypes. Blood. 2019;

Rys RN, Venkataraman M, Zeng J, Mann KK, Johnson N. Fas Mutations in Non-Hodgkin’s Lymphoma (NHL): Implications for Disease Progression and Therapeutic Resistance. Blood [Internet]. 2019 Nov [cited 2024 Dec 17];134(Supplement_1):1520–1520. Available from: https://ashpublications.org/blood/article/134/Supplement_1/1520/427201/Fas-Mutations-in-NonHodgkins-Lymphoma-NHL

Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC, Park AY, Yin Q, Damko E, Jang SB, Raunser S, Robinson CV, Siegel RM, Walz T, Wu H. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat Struct Mol Biol. 2010 Nov;17(11):1324–1329. PMCID: PMC2988912

Spina V, Khiabanian H, Messina M, Monti S, Cascione L, Bruscaggin A, Spaccarotella E, Holmes AB, Arcaini L, Lucioni M, Tabbò F, Zairis S, Diop F, Cerri M, Chiaretti S, Marasca R, Ponzoni M, Deaglio S, Ramponi A, Tiacci E, Pasqualucci L, Paulli M, Falini B, Inghirami G, Bertoni F, Foà R, Rabadan R, Gaidano G, Rossi D. The genetics of nodal marginal zone lymphoma. Blood. 2016 Sep 8;128(10):1362–1373. PMCID: PMC5016706