EZH2
[[TOC]]
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.[@morinSomaticMutationsAltering2010] 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.[@yapSomaticMutationsEZH22011] 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.[@scholzeCombinedEZH2Bcl22020]
| Entity | Tier | Description |
|---|---|---|
 |
1 | high-confidence MZL gene |
 |
1 | high-confidence PMBL/cHL/GZL gene[@mottokIntegrativeGenomicAnalysis2019] |
 |
1 | high-confidence DLBCL gene supported by functional data [@morinSomaticMutationsAltering2010] |
 |
1 | high-confidence FL gene supported by functional data [@morinSomaticMutationsAltering2010] |
 |
2 | relevance in BL not firmly established[@loveGeneticLandscapeMutations2012] |
include:DLBCL_EZH2.md include:FL_EZH2.md
| 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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