CREBBP.md
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@@ -13,7 +13,7 @@ This gene has some recurrent sites of mutations (hotspots), mostly in the HAT do
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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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+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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## History
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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-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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+|![DLBCL](images/icons/DLBCL_tier1.png) |1-EE |high-confidence DLBCL gene supported by functional data[@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
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+|![FL](images/icons/FL_tier1.png) |1-EE |high-confidence FL gene supported by functional data[@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)
DLBCL_genes.md
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@@ -36,7 +36,7 @@ link-citations: true
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|[CD79B](CD79B)|1|[Morin et al](papers/morinFrequentMutationHistonemodifying2011)[@morinFrequentMutationHistonemodifying2011]|[@paneaWholeGenomeLandscape2019]|
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|[CD83](CD83)|1, aSHM|[Morin et al](papers/morinMutationalStructuralAnalysis2013)[@morinMutationalStructuralAnalysis2013]|[@paneaWholeGenomeLandscape2019; @dunsCharacterizationDLBCLPMBL2021b; @russler-germainMutationsAssociatedProgression2023b]|
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|[CDKN2A](CDKN2A)|1|[Morin et al](papers/morinMutationalStructuralAnalysis2013)[@morinMutationalStructuralAnalysis2013]|[@spinaGeneticsNodalMarginal2016b; @grandeGenomewideDiscoverySomatic2019]|
39
-|[CREBBP](CREBBP)|1|[Pasqualucci et al](papers/pasqualucciInactivatingMutationsAcetyltransferase2011a)[@pasqualucciInactivatingMutationsAcetyltransferase2011a]|[@parryWholeExomeSequencing2013; @dunsCharacterizationDLBCLPMBL2021b; @loveGeneticLandscapeMutations2012]|
39
+|[CREBBP](CREBBP)|1-EE|[Pasqualucci et al](papers/pasqualucciInactivatingMutationsAcetyltransferase2011a)[@pasqualucciInactivatingMutationsAcetyltransferase2011a]|[@parryWholeExomeSequencing2013; @dunsCharacterizationDLBCLPMBL2021b; @loveGeneticLandscapeMutations2012]|
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|[CXCR4](CXCR4)|1, aSHM|[Khodabakhshi et al](papers/khodabakhshiRecurrentTargetsAberrant2012)[@khodabakhshiRecurrentTargetsAberrant2012]|[@paneaWholeGenomeLandscape2019; @krysiakRecurrentSomaticMutations2017b]|
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|[CXCR5](CXCR5)|1|[Schmitz et al](papers/schmitzGeneticsPathogenesisDiffuse2018a)[@schmitzGeneticsPathogenesisDiffuse2018a]|[@mottokIntegrativeGenomicAnalysis2019b]|
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|[DDX3X](DDX3X)|1|[Schmitz et al](papers/schmitzGeneticsPathogenesisDiffuse2018a)[@schmitzGeneticsPathogenesisDiffuse2018a]|[@mottokIntegrativeGenomicAnalysis2019b; @schmitzBurkittLymphomaPathogenesis2012]|
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@@ -47,7 +47,7 @@ link-citations: true
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|[EP300](EP300)|1|[Pasqualucci et al](papers/pasqualucciInactivatingMutationsAcetyltransferase2011a)[@pasqualucciInactivatingMutationsAcetyltransferase2011a]|[@paneaWholeGenomeLandscape2019; @rossiCodingGenomeSplenic2012c]|
48 48
|[ETS1](ETS1)|1, aSHM|[Morin et al](papers/morinFrequentMutationHistonemodifying2011)[@morinFrequentMutationHistonemodifying2011]|[@paneaWholeGenomeLandscape2019]|
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|[ETV6](ETV6)|1, aSHM|[Lohr et al](papers/lohrDiscoveryPrioritizationSomatic2012a)[@lohrDiscoveryPrioritizationSomatic2012a]||
50
-|[EZH2](EZH2)|1|[Morin et al](papers/morinSomaticMutationsAltering2010a)[@morinSomaticMutationsAltering2010a]|[@loveGeneticLandscapeMutations2012; @mottokIntegrativeGenomicAnalysis2019b]|
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+|[EZH2](EZH2)|1-EE|[Morin et al](papers/morinSomaticMutationsAltering2010a)[@morinSomaticMutationsAltering2010a]|[@loveGeneticLandscapeMutations2012; @mottokIntegrativeGenomicAnalysis2019b]|
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|[FAS](FAS)|1|[Scholl et al](papers/schollMutationsRegionFAS2007)[@schollMutationsRegionFAS2007]|[@spinaGeneticsNodalMarginal2016b]|
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|[FBXO11](FBXO11)|1|[Hubschmann et al](papers/hubschmannMutationalMechanismsShaping2021b)[@hubschmannMutationalMechanismsShaping2021b]|[@richterRecurrentMutationID32012a; @parryWholeExomeSequencing2013]|
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|[FBXW7](FBXW7)|1|[Zhang et al](papers/zhangGeneticHeterogeneityDiffuse2013)[@zhangGeneticHeterogeneityDiffuse2013]||
EP300.md
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# EP300
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## Overview
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-Mutations in EP300 are significant contributors to the pathogenesis and progression of B-cell lymphomas such as DLBCL and FL. These mutations impair histone acetylation, disrupt epigenetic gene regulation. 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.<sup>1,2</sup> 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.<sup>3</sup>
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+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]
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+
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+## Experimental Evidence
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+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]
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+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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## History
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