Table of Contents

Overview

Mutations in this gene were first described in MZL by Braggio et al.1 then in MCL by Bea et al.2 ATM mutations were later described in DLBCL by Reddy et al.3 Although there is experimental data supporting the role of loss-of-function mutations in MCL biology, the relevance of ATM mutations in DLBCL remains unclear. Selective pressure analysis did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers.

Experimental Evidence

Driver mutations affecting this gene in MCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).4

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL gene
MCL 1 High-confidence MCL gene
MZL 1 High-confidence MZL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

MCL

pathology Collection N mutated Incidence CI
MCL GAMBL 160 75 0.4634 [0.3877,0.539]
MCL BC_MCL 103 56 0.5437 [0.4475,0.6399]
MCL Barcelona 57 19 0.3333 [0.211,0.4557]

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 52 0.0478 [0.0351,0.0604]
DLBCL GAMBL with Reddy 2,088 111 0.0532 [0.0435,0.0628]
DLBCL BC 231 10 0.0433 [0.017,0.0695]
DLBCL Dana-Farber 303 13 0.0429 [0.0201,0.0657]
DLBCL NCI 470 26 0.0553 [0.0347,0.076]
DLBCL Reddy 999 59 0.0591 [0.0444,0.0737]
DLBCL DLBCL_ICGC 85 3 0.0353 [0,0.0745]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 8 0.0221 [0.0058,0.0385]
BL GAMBL without ICGC/Zhou 320 11 0.0241 [0.0074,0.0408]
BL GAMBL with Panea 410 15 0.0268 [0.0112,0.0423]
BL BLGSP 219 4 0.0183 [5e-04,0.036]
BL Zhou/ICGC 90 4 0.0444 [0.0019,0.087]
BL Panea 101 7 0.0693 [0.0198,0.1188]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 14 0.0218 [0.0105,0.0331]
FL GAMBL with Crouch 1,189 43 0.0362 [0.0256,0.0468]
FL BC 379 5 0.0132 [0.0017,0.0247]
FL Kalmbach 164 7 0.0427 [0.0117,0.0736]
FL Crouch 547 29 0.0530 [0.0342,0.0718]
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 1.4494 0.0000 1.0000
FL 1.0522 2.7469 1.0000
DLBCL 0.9413 1.0068 0.9986

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012 : Braggio : MZL 2013 : Beà : MCL 2017-10-10 : Reddy : DLBCL 2018-10-01 : Arthur : DLBCL 2020-07-01: Fan : DLBCL

References

1.
Braggio E, Dogan A, Keats JJ, Chng WJ, Huang G, Matthews JM, Maurer MJ, Law ME, Bosler DS, Barrett M, Lossos IS, Witzig TE, Fonseca R. Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities. Mod Pathol. 2012 May;25(5):651–660. PMCID: PMC3341516
2.
Beà S, Valdés-Mas R, Navarro A, Salaverria I, Martín-Garcia D, Jares P, Giné E, Pinyol M, Royo C, Nadeu F, Conde L, Juan M, Clot G, Vizán P, Croce LD, Puente DA, López-Guerra M, Moros A, Roue G, Aymerich M, Villamor N, Colomo L, Martínez A, Valera A, Martín-Subero JI, Amador V, Hernández L, Rozman M, Enjuanes A, Forcada P, Muntañola A, Hartmann EM, Calasanz MJ, Rosenwald A, Ott G, Hernández-Rivas JM, Klapper W, Siebert R, Wiestner A, Wilson WH, Colomer D, López-Guillermo A, López-Otín C, Puente XS, Campo E. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. PNAS. 2013;110(45):18250–18255.
3.
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
4.
Camacho E, Hernández L, Hernández S, Tort F, Bellosillo B, Beà S, Bosch F, Montserrat E, Cardesa A, Fernández PL, Campo E. ATM gene inactivation in mantle cell lymphoma mainly occurs by truncating mutations and missense mutations involving the phosphatidylinositol-3 kinase domain and is associated with increasing numbers of chromosomal imbalances. Blood. 2002 Jan 1;99(1):238–244.
5.
Fan Z, Pei R, Sha K, Chen L, Wang T, Lu Y. Comprehensive characterization of driver genes in diffuse large B cell lymphoma. Oncol Lett. 2020 Jul;20(1):382–390. PMCID: PMC7285964
6.
Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, Mottok A, Hilton LK, Lat PK, Zhao EY, Culibrk L, Ennishi D, Jessa S, Chong L, Thomas N, Pararajalingam P, Meissner B, Boyle M, Davidson J, Bushell KR, Lai D, Farinha P, Slack GW, Morin GB, Shah S, Sen D, Jones SJM, Mungall AJ, Gascoyne RD, Audas TE, Unrau P, Marra MA, Connors JM, Steidl C, Scott DW, Morin RD. Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma. Nat Commun. 2018 Oct 1;9(1):4001. PMCID: PMC6167379

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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