KMT2C

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

History

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

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene
	2	relevance in BL not firmly established
	1	high-confidence DLBCL gene
	2	relevance in MCL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	3.25
DLBCL	Schmitz cohort	8.30
DLBCL	Reddy cohort	7.31
DLBCL	Chapuy cohort	6.41
BL	GAMBL genomes+capture	6.47
BL	Thomas cohort	NA
BL	Panea cohort	NA
MCL	GAMBL genomes	0.47

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	No	0.628	0.000
DLBCL	No	No	1.569	1.911
FL	No	No	0.550	0.000

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

References

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. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1398-403. doi: 10.1073/pnas.1205299110. Epub 2013 Jan 4. PMID: 23292937; PMCID: PMC3557051.
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 5;171(2):481-494.e15. doi: 10.1016/j.cell.2017.09.027. PMID: 28985567; PMCID: PMC5659841.
https://pubpeer.com/publications/C1086AC68FD7082E3811E097EA4EA0
Lee MJ, Koff JL, Switchenko JM, Jhaney CI, Harkins RA, Patel SP, Dave SS, Flowers CR. Genome-defined African ancestry is associated with distinct mutations and worse survival in patients with diffuse large B-cell lymphoma. Cancer. 2020 Aug 1;126(15):3493-3503. doi: 10.1002/cncr.32866. Epub 2020 May 29. PMID: 32469082; PMCID: PMC7494053.
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):2988-96. doi: 10.1182/blood-2013-07-517177. Epub 2014 Mar 28. PMID: 24682267; PMCID: PMC4014841. ## KMT2C Expression