EP300

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bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true

[[TOC]]

Overview

Mutations in EP300 are significant contributors to the pathogenesis and progression of B-cell lymphomas such as DLBCL and FL.[@pasqualucciInactivatingMutationsAcetyltransferase2011] 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.[@pasqualucciInactivatingMutationsAcetyltransferase2011]

Experimental Evidence

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.[@pasqualucciInactivatingMutationsAcetyltransferase2011; @veazeyCARM1InhibitionReduces2020] 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.[@nieGenomewideCRISPRScreens2021]

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence MZL gene[@rossiCodingGenomeSplenic2012]
	1	high-confidence DLBCL gene supported by functional data [@pasqualucciInactivatingMutationsAcetyltransferase2011]
	1	high-confidence FL gene supported by functional data [@pasqualucciInactivatingMutationsAcetyltransferase2011]

Mutation incidence in large patient cohorts (GAMBL reanalysis)

include:DLBCL_EP300.md include:FL_EP300.md

Mutation pattern and selective pressure estimates

include:dnds_EP300.md

EP300 Hotspots

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

include:browser_EP300.md

Expression

include:mermaid_EP300.md

References