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^{sarkozyMutationalLandscapeGray2021a?}
	2	relevance in BL not firmly established¹
	1	high-confidence DLBCL gene²
	2	relevance in MCL not firmly established³

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

KMT2C Expression

References

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

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

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.