Table of Contents

Overview

ARID1A (AT-rich interactive domain-containing protein 1A) is a gene that encodes a subunit of the SWI/SNF chromatin remodeling complex, which is involved in regulating DNA accessibility. Mutations in ARID1A are implicated in various cancers, including B-cell lymphomas. They are the most abundant in Burkitt lymphoma but also occur in FL and, to a lesser extent, DLBCL. Overall, components of SWI/SNF have been identified as an emerging theme in germinal centre-derived B-cell lymphomas but their role has not been thoroughly elucidated.1

Experimental Evidence

Driver mutations affecting this gene have been experimentally demonstrated to cause a reduction or loss of function (LOF).2

Relevance tier by entity

Entity Tier Description
BL 1 High-confidence BL gene
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
MZL 1 High-confidence MZL gene
PMBL 1 High-confidence PMBL gene

Mutation incidence in large cohorts

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 76 0.0698 [0.0547,0.0849]
DLBCL GAMBL with Reddy 2,088 120 0.0575 [0.0475,0.0675]
DLBCL BC 231 16 0.0693 [0.0365,0.102]
DLBCL Dana-Farber 303 12 0.0396 [0.0176,0.0616]
DLBCL NCI 470 42 0.0894 [0.0636,0.1152]
DLBCL Reddy 999 44 0.0440 [0.0313,0.0568]
DLBCL DLBCL_ICGC 85 6 0.0706 [0.0161,0.125]
pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 67 0.1044 [0.0807,0.128]
FL GAMBL with Crouch 1,189 140 0.1177 [0.0994,0.1361]
FL BC 379 40 0.1055 [0.0746,0.1365]
FL Kalmbach 164 15 0.0915 [0.0473,0.1356]
FL Crouch 547 73 0.1335 [0.105,0.162]
FL FL_ICGC 99 12 0.1212 [0.0569,0.1855]
pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 95 0.3005 [0.2498,0.3513]
BL GAMBL without ICGC/Zhou 320 95 0.2854 [0.2365,0.3342]
BL GAMBL with Panea 410 115 0.2699 [0.2274,0.3124]
BL BLGSP 219 75 0.3425 [0.2796,0.4053]
BL Zhou/ICGC 90 20 0.2222 [0.1363,0.3081]
BL Panea 101 20 0.1980 [0.1203,0.2757]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 2.8939 119.1677 0
FL 1.2336 76.5180 0
DLBCL 0.8865 10.0620 0

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 2012-08-27 : Rossi : MZL 2012-12-01 : Love : BL 2013-01-01 : Zhang : DLBCL 2017-05-01 : Albuquerque : DLBCL 2017-01-26 : Krysiak : FL 2018-04-12 : Schmitz : DLBCL 2018-10-01 : Arthur : DLBCL 2019-12-10 : Wienand : PMBL

References

1.
Lunning MA, Green MR. Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas. Blood Cancer J. 2015 Oct 16;5(10):e361. PMCID: PMC4635197
2.
Barisic D, Chin CR, Meydan C, Teater M, Tsialta I, Mlynarczyk C, Chadburn A, Wang X, Sarkozy M, Xia M, Carson SE, Raggiri S, Debek S, Pelzer B, Durmaz C, Deng Q, Lakra P, Rivas M, Steidl C, Scott DW, Weng AP, Mason CE, Green MR, Melnick A. ARID1A orchestrates SWI/SNF-mediated sequential binding of transcription factors with ARID1A loss driving pre-memory B cell fate and lymphomagenesis. Cancer Cell. 2024 Apr 8;42(4):583–604.e11.
3.
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
4.
Krysiak K, Gomez F, White BS, Matlock M, Miller CA, Trani L, Fronick CC, Fulton RS, Kreisel F, Cashen AF, Carson KR, Berrien-Elliott MM, Bartlett NL, Griffith M, Griffith OL, Fehniger TA. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood. 2017 Jan 26;129(4):473–483. PMCID: PMC5270390
5.
Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WWL, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SS. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012 Dec;44(12):1321–1325. PMCID: PMC3674561
6.
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
7.
Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Famà R, Ciardullo C, Greco M, Cresta S, Piranda D, Holmes A, Fabbri G, Messina M, Rinaldi A, Wang J, Agostinelli C, Piccaluga PP, Lucioni M, Tabbò F, Serra R, Franceschetti S, Deambrogi C, Daniele G, Gattei V, Marasca R, Facchetti F, Arcaini L, Inghirami G, Bertoni F, Pileri SA, Deaglio S, Foà R, Dalla-Favera R, Pasqualucci L, Rabadan R, Gaidano G. The coding genome of splenic marginal zone lymphoma: Activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med. 2012 Aug 27;209(9):1537–1551. PMCID: PMC3428941
8.
Wienand K, Chapuy B, Stewart C, Dunford AJ, Wu D, Kim J, Kamburov A, Wood TR, Cader FZ, Ducar MD, Thorner AR, Nag A, Heubeck AT, Buonopane MJ, Redd RA, Bojarczuk K, Lawton LN, Armand P, Rodig SJ, Fromm JR, Getz G, Shipp MA. Genomic analyses of flow-sorted Hodgkin Reed-Sternberg cells reveal complementary mechanisms of immune evasion. Blood Adv. 2019 Dec 10;3(23):4065–4080. PMCID: PMC6963251
9.
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

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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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