Table of Contents

Overview

This gene has been reported to be recurrently mutated in DLBCL. The rate of mutations in KMT2C (MLL3) varies across published cohorts. In the initial study describing these mutations, it was suggested to be mutated in >15% of DLBCLs.1 The actual rate of mutations may be much lower,2 potentially due to the existence of germline variants in some studies.3 A more recent study suggested KMT2C mutations were more common in DLBCLs in patients of African ancestry.4 Although KMT2C mutations have been described as a feature of MCL in a single study, this pattern was not reproduced in other cohorts.5

Relevance tier by entity

Entity Tier Description
BL 2 Role of KMT2C mutations in BL requires confirmation
DLBCL 1 High-confidence DLBCL gene
MCL 2 Role of KMT2C mutations in MCL requires confirmation
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 65 0.0597 [0.0456,0.0738]
DLBCL GAMBL with Reddy 2,088 138 0.0661 [0.0554,0.0767]
DLBCL BC 231 6 0.0260 [0.0055,0.0465]
DLBCL Dana-Farber 303 16 0.0528 [0.0276,0.078]
DLBCL NCI 470 39 0.0830 [0.058,0.1079]
DLBCL Reddy 999 73 0.0731 [0.0569,0.0892]
DLBCL DLBCL_ICGC 85 4 0.0471 [0.002,0.0921]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 6 0.0175 [0.0029,0.0321]
BL GAMBL without ICGC/Zhou 320 22 0.0328 [0.0137,0.0519]
BL GAMBL with Panea 410 23 0.0233 [0.009,0.0376]
BL BLGSP 219 5 0.0228 [0.003,0.0426]
BL Zhou/ICGC 90 1 0.0111 [0,0.0328]
BL Panea 101 17 0.1683 [0.0953,0.2413]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 0.5410 0.0000 1.0000
FL 0.8804 0.0000 1.0000
DLBCL 1.0823 1.1361 0.9986

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Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2013-01-01 : Zhang : DLBCL 2014-05-08 : Zhang : MCL 2017-10-10 : Reddy : DLBCL 2019-07-23 : Zhou : BL 2021-04-01 : Sarkozy : PMBL

References

1.
Sarkozy C, Hung SS, Chavez EA, Duns G, Takata K, Chong LC, Aoki T, Jiang A, Miyata-Takata T, Telenius A, Slack GW, Molina TJ, Ben-Neriah S, Farinha P, Dartigues P, Damotte D, Mottok A, Salles GA, Casasnovas RO, Savage KJ, Laurent C, Scott DW, Traverse-Glehen A, Steidl C. Mutational landscape of gray zone lymphoma. Blood. 2021 Apr 1;137(13):1765–1776.
2.
Zhou P, Blain AE, Newman AM, Zaka M, Chagaluka G, Adlar FR, Offor UT, Broadbent C, Chaytor L, Whitehead A, Hall A, O’Connor H, Van Noorden S, Lampert I, Bailey S, Molyneux E, Bacon CM, Bomken S, Rand V. Sporadic and endemic Burkitt lymphoma have frequent FOXO1 mutations but distinct hotspots in the AKT recognition motif. Blood Adv. 2019 Jul 23;3(14):2118–2127. PMCID: PMC6650741
3.
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
4.
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
5.
Zhang J, Jima D, Moffitt AB, Liu Q, Czader M, Hsi ED, Fedoriw Y, Dunphy CH, Richards KL, Gill JI, Sun Z, Love C, Scotland P, Lock E, Levy S, Hsu DS, Dunson D, Dave SS. The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells. Blood. 2014 May 8;123(19):2988–2996.

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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