EZH2 - morinlab/LLMPP GitHub Wiki
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 |
---|---|---|
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1 | high-confidence MZL gene |
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1 | high-confidence PMBL/cHL/GZL gene[@mottokIntegrativeGenomicAnalysis2019b] |
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1-EE | high-confidence DLBCL gene supported by functional data [@morinSomaticMutationsAltering2010a] |
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1-EE | high-confidence FL gene supported by functional data [@morinSomaticMutationsAltering2010a] |
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2 | relevance in BL not firmly established[@loveGeneticLandscapeMutations2012] |
Entity | source | frequency (%) |
---|---|---|
BL | GAMBL genomes+capture | 3.46 |
BL | Thomas cohort | 1.30 |
BL | Panea cohort | 10.90 |
DLBCL | GAMBL genomes | 13.77 |
DLBCL | Schmitz cohort | 9.15 |
DLBCL | Reddy cohort | 8.91 |
DLBCL | Chapuy cohort | 5.56 |
FL | GAMBL genomes | 24.94 |
Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
---|---|---|---|---|
BL | No | No | 4.992 | 0 |
DLBCL | No | Yes | 19.753 | 0 |
FL | No | Yes | 117.987 | 0 |
Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
---|---|---|---|
chr7 | 148508745 | T>C | N640S |
chr7 | 148508740 | A>G | F642L |
chr7 | 148508728 | A>T | Y646N |
chr7 | 148508728 | A>G | Y646H |
chr7 | 148508727 | T>G | Y646S |
chr7 | 148508727 | T>C | Y646C |
chr7 | 148508727 | T>A | Y646F |
chr7 | 148506466 | TG>GC | A682G |
chr7 | 148506467 | G>C | A682G |
chr7 | 148506437 | GC>AA | A692L |
chr7 | 148506437 | G>A | A692V |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
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