EP300
Mutations in EP300 are significant contributors to the pathogenesis and progression of B-cell lymphomas such as DLBCL and FL.[@pasqualucciInactivatingMutationsAcetyltransferase2011a] This gene has some recurrent sites of mutations (hot spots), which typically impact its HAT domain, a region crucial for acetylating histones and non-histone proteins.[@pasqualucciInactivatingMutationsAcetyltransferase2011a]
EP300 mutations impair histone acetylation, disrupt epigenetic gene regulation. Mutations in CREBBP and EP300 affect a common pathway and have been described as mutually exclusive due to some functional redundancy.[@pasqualucciInactivatingMutationsAcetyltransferase2011a; @veazeyCARM1InhibitionReduces2020b] Studies using genome-wide CRISPR-Cas9 screens have identified synthetic lethal interactions between CREBBP and EP300, suggesting that targeting one may affect the viability of cells with mutations in the other.[@nieGenomewideCRISPRScreens2021b]
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timeline
title Publication timing
2011-03-10 : Pasqualucci : FL
2012-08-27 : Rossi : MZL
2017-10-10 : Reddy : DLBCL
2018-04-12 : Schmitz : DLBCL
2018-05-01 : Chapuy : DLBCL
2018-10-01 : Arthur : DLBCL
| Entity | Tier | Description |
|---|---|---|
 |
1 | high-confidence MZL gene[@rossiCodingGenomeSplenic2012c] |
 |
1-EE | high-confidence DLBCL gene supported by functional data [@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
 |
1-EE | high-confidence FL gene supported by functional data [@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
| Entity | source | frequency (%) |
|---|---|---|
| BL | GAMBL genomes+capture | 4.62 |
| BL | Thomas cohort | 4.20 |
| BL | Panea cohort | 7.90 |
| DLBCL | GAMBL genomes | 11.85 |
| DLBCL | Schmitz cohort | 9.79 |
| DLBCL | Reddy cohort | 7.11 |
| DLBCL | Chapuy cohort | 8.12 |
| FL | GAMBL genomes | 12.47 |
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | No | No | 2.769 | 3.550 |
| DLBCL | No | No | 3.344 | 7.980 |
| FL | No | Yes | 15.586 | 7.719 |
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr22 | 41566459 | T>C | Y1446H |
| chr22 | 41566460 | A>G | Y1446C |
| chr22 | 41566460 | A>C | Y1446S |
| chr22 | 41566462 | A>T | I1447F |
| chr22 | 41566466 | T>G | F1448C |
| chr22 | 41566474 | C>T | H1451Y |
| chr22 | 41566476 | T>G | H1451Q |
| chr22 | 41566478 | C>T | P1452L |
| chr22 | 41566486 | C>G | Q1455E |
| chr22 | 41566487 | A>G | Q1455R |
| chr22 | 41566488 | G>T | Q1455H |
| chr22 | 41566495 | C>T | P1458S |
| chr22 | 41566495 | C>A | P1458T |
| chr22 | 41566496 | C>T | P1458L |
| chr22 | 41566511 | T>C | L1463P |
| chr22 | 41566511 | T>G | L1463R |
| chr22 | 41566519 | T>G | W1466G |
| chr22 | 41566519 | T>A | W1466R |
| chr22 | 41566519 | T>C | W1466R |
| chr22 | 41566520 | G>T | W1466L |
| chr22 | 41566521 | G>C | W1466C |
| chr22 | 41566522 | T>A | Y1467N |
| chr22 | 41566522 | T>C | Y1467H |
| chr22 | 41566522 | T>G | Y1467D |
| chr22 | 41566523 | A>G | Y1467C |
| chr22 | 41566523 | A>T | Y1467F |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
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