CREBBP.md
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# CREBBP
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## Overview
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-CREBBP mutations are highly prevalent in both DLBCL and FL.[@pasqualucciInactivatingMutationsAcetyltransferase2011a] These mutations often affect the histone acetyltransferase (HAT) domain, crucial for regulating gene expression through chromatin modification, or generate a truncated protein.[@pasqualucciInactivatingMutationsAcetyltransferase2011a]
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+CREBBP mutations are highly prevalent in both DLBCL and FL.[@pasqualucciInactivatingMutationsAcetyltransferase2011a]
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This gene has some recurrent sites of mutations (hotspots), mostly in the HAT domain. The pattern of mutations in DLBCL is distinct from FL with the latter having more HAT domain mutations relative to truncating mutations.[@drevalGeneticSubdivisionsFollicular2023]
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+## Experimental Evidence
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+CREBBP missense mutations often affect the histone acetyltransferase (HAT) domain, crucial for regulating gene expression through chromatin modification, or generate a truncated protein.[@pasqualucciInactivatingMutationsAcetyltransferase2011a]
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+In a transgenic mouse model, CREBBP loss cooperated with BCL2 overexpression to promote B-cell lymphomagenesis.[@garcia-ramirezCrebbpLossCooperates2017]
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+Mutations in CREBBP and EP300 affect a common pathway and have been described as mutually exclusive due to some functional redundancy.[@pasqualucciInactivatingMutationsAcetyltransferase2011a; @veazeyCARM1InhibitionReduces2020b]
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## History
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```mermaid
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|:------:|:----:|--------------------------------------|
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|![MZL](images/icons/MZL_tier2.png)|2|relevance in MZL not firmly established[@parryWholeExomeSequencing2013] |
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|![PMBL](images/icons/PMBL_tier1.png)|1|high-confidence PMBL/cHL/GZL gene[@dunsCharacterizationDLBCLPMBL2021b] |
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-|![DLBCL](images/icons/DLBCL_tier1.png) |1 |high-confidence DLBCL gene[@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
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-|![FL](images/icons/FL_tier1.png) |1 |high-confidence FL gene[@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
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+|![DLBCL](images/icons/DLBCL_tier1.png) |1-EE |high-confidence DLBCL gene[@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
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+|![FL](images/icons/FL_tier1.png) |1-EE |high-confidence FL gene[@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
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|![BL](images/icons/BL_tier2.png) |2 |association with BL is tenuous[@loveGeneticLandscapeMutations2012]|
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## Mutation incidence in large patient cohorts (GAMBL reanalysis)