EZH2 encodes a histone methyltransferase that is a component of the polycomb repressive complex 2 (PRC2). This gene is recurrently mutated in both FL and DLBCL and has a common mutation hot spot (Y646) that affects the SET domain.[@morinSomaticMutationsAltering2010a] EZH2 mutations are one of the defining features of the EZB genetic subgroup of DLBCL.[@wrightProbabilisticClassificationTool2020] Although mutations in EZH2 have been described in some BL patients, they are extremely rare in most BL cohorts that have been sequenced.[@loveGeneticLandscapeMutations2012; @thomasGeneticSubgroupsInform2023]

Mutations at the main hotspot and some less common hotspots lead to enhanced methylation by PRC2.[@yapSomaticMutationsEZH22011b] A number of small molecule/pharmacologic inhibitors of EZH2 activity have been described.[@garapaty-raoIdentificationEZH2EZH12013; @knutsonSelectiveInhibitionEZH22014] At least one of these, tazemetostat, has shown benefit in FL.[@morinTreatingLymphomaNow2021] Combination therapies including EZH2 inhibitors are also under exploration for DLBCL patients with mutant EZH2.[@scholzeCombinedEZH2Bcl22020b]

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timeline
    title Publication timing
      2010-02-02 : Morin : DLBCL
      2012-03-06 : Lohr : DLBCL
      2012-12-01 : Love : BL
2013-01-01 : Zhang : DLBCL
2013-08-15 : Morin : DLBCL
      2019-09-05 : Mottok : PMBL

Entity	Tier	Description
	1	high-confidence MZL gene
	1	high-confidence PMBL/cHL/GZL gene[@mottokIntegrativeGenomicAnalysis2019b]
	1-EE	high-confidence DLBCL gene supported by functional data [@morinSomaticMutationsAltering2010a]
	1-EE	high-confidence FL gene supported by functional data [@morinSomaticMutationsAltering2010a]
	2	relevance in BL not firmly established[@loveGeneticLandscapeMutations2012]

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

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