3e2d35193ac51756bd54a058abe7102ae74af099
CCNF.md
| ... | ... | @@ -18,7 +18,7 @@ timeline |
| 18 | 18 | |
| 19 | 19 | |Entity|Tier|Description | |
| 20 | 20 | |:------:|:----:|--------------------------------------| |
| 21 | -| |2 |relevance in BL not firmly established[@abateDistinctViralMutational2015a]| |
|
| 21 | +| |2 |relevance in BL not firmly established[@abateDistinctViralMutational2015]| |
|
| 22 | 22 | |
| 23 | 23 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 24 | 24 |
CD58.md
| ... | ... | @@ -12,7 +12,7 @@ CD58, also known as lymphocyte function-associated antigen 3 (LFA-3), is crucial |
| 12 | 12 | ## Experimental Evidence |
| 13 | 13 | |
| 14 | 14 | In DLBCL, mutations prevent the expression of CD58 on the cell surface, impairing the ability of T and NK cells to recognize and attack the tumor cells. |
| 15 | -This is often accompanied by mutations in the β2-Microglobulin gene, which further aids in immune evasion.[@challa-malladiCombinedGeneticInactivationa] |
|
| 15 | +This is often accompanied by mutations in the β2-Microglobulin gene, which further aids in immune evasion.[@challa-malladiCombinedGeneticInactivation2011] |
|
| 16 | 16 | |
| 17 | 17 | ## History |
| 18 | 18 | ```mermaid |
CD70.md
| ... | ... | @@ -10,7 +10,7 @@ CD70 is a costimulatory molecule expressed on some activated lymphocytes and has |
| 10 | 10 | CD70 aberrations are relatively common in DLBCL and appear more frequent in certain DLBCL patient populations. For instance, in a Chinese DLBCL cohort, 24% of cases exhibited CD70 genetic changes, compared to 10.8% in a Swedish cohort.[@nieDualRoleCD702022b] |
| 11 | 11 | CD70 mutations are associated with the BN2 genetic subtype of DLBCL.[@wrightProbabilisticClassificationTool2020] |
| 12 | 12 | The mutation pattern in CD70 is consistent with the preferential accumulation of *inactivating mutations*. |
| 13 | -Genetic perturbation limits the development of an effective CD8+ T-cell immune response in Bcl6-driven DLBCL. [@nieDualRoleCD702022b] |
|
| 13 | +Genetic perturbation limits the development of an effective CD8+ T-cell immune response in Bcl6-driven DLBCL. [@nieDualRoleCD702022] |
|
| 14 | 14 | In mouse models, CD70 loss promoted lymphomagenesis, consistent with its role as a tumor suppressor gene in B-cell lymphomas.[@mandatoAbstractA38Cd702022] |
| 15 | 15 | |
| 16 | 16 | ## History |
| ... | ... | @@ -33,7 +33,7 @@ timeline |
| 33 | 33 | |Entity|Tier|Description | |
| 34 | 34 | |:------:|:----:|--------------------------------------| |
| 35 | 35 | | |1 |high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011]| |
| 36 | -| |2 |relevance in FL not firmly established[@russler-germainMutationsAssociatedProgression2023b]| |
|
| 36 | +| |2 |relevance in FL not firmly established[@russler-germainMutationsAssociatedProgression2023]| |
|
| 37 | 37 | |
| 38 | 38 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 39 | 39 |
CD79A.md
| ... | ... | @@ -19,8 +19,8 @@ timeline |
| 19 | 19 | |
| 20 | 20 | |Entity|Tier|Description | |
| 21 | 21 | |:------:|:----:|--------------------------------------| |
| 22 | -||2|relevance in MZL not firmly established[@rossiCodingGenomeSplenic2012c]| |
|
| 23 | -| |2 |relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022b]| |
|
| 22 | +||2|relevance in MZL not firmly established[@rossiCodingGenomeSplenic2012]| |
|
| 23 | +| |2 |relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022]| |
|
| 24 | 24 | |
| 25 | 25 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 26 | 26 |
CD79B.md
| ... | ... | @@ -10,7 +10,7 @@ CD79B mutations significantly contribute to the pathogenesis of DLBCL by enhanci |
| 10 | 10 | These mutations, especially when co-occurring with MYD88 mutations, define a unique molecular subtype.[@wrightProbabilisticClassificationTool2020] |
| 11 | 11 | This has clinical and therapeutic implications as it may contribute sensitivity to BTK inhibitors. |
| 12 | 12 | In an inducible mouse model of MYD88-driven DLBCL, CD79B mutations did not accelerate lymphomagenesis but demonstrated an increased sensitivity to pharmacological BTK inhibition.[@flumannInducibleCd79bMutation2024] |
| 13 | -In a retrospective analysis, younger patients with MCD DLBCL that were treated with ibrutinib had significantly better outcomes.[@wilsonEffectIbrutinibRCHOP2021b] |
|
| 13 | +In a retrospective analysis, younger patients with MCD DLBCL that were treated with ibrutinib had significantly better outcomes.[@wilsonEffectIbrutinibRCHOP2021] |
|
| 14 | 14 | The most common hotspot mutation in CD79B is at the tyrosine residue 196 (Y196). |
| 15 | 15 | This and other common mutations primarily occur in the immunoreceptor tyrosine-based activation motif (ITAM) domain and prevent the negative regulatory feedback provided by Lyn kinase thereby enhancing BCR signaling.[@kimCD79BMYD88Mutations2014; @davisChronicActiveBcellreceptor2010] |
| 16 | 16 |
CD83.md
| ... | ... | @@ -33,9 +33,9 @@ timeline |
| 33 | 33 | |
| 34 | 34 | |Entity|Tier|Description | |
| 35 | 35 | |:------:|:----:|--------------------------------------| |
| 36 | -||1|high-confidence PMBL/cHL/GZL gene[@dunsCharacterizationDLBCLPMBL2021b]| |
|
| 36 | +||1|high-confidence PMBL/cHL/GZL gene[@dunsCharacterizationDLBCLPMBL2021]| |
|
| 37 | 37 | | |1-a | aSHM target and high-confidence DLBCL gene [@morinMutationalStructuralAnalysis2013; @schmitzGeneticsPathogenesisDiffuse2018a; @reddyGeneticFunctionalDrivers2017]| |
| 38 | -| |1-a | aSHM target and high-confidence FL gene [@russler-germainMutationsAssociatedProgression2023b]| |
|
| 38 | +| |1-a | aSHM target and high-confidence FL gene [@russler-germainMutationsAssociatedProgression2023]| |
|
| 39 | 39 | | |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@paneaWholeGenomeLandscape2019]| |
| 40 | 40 | |
| 41 | 41 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CDC42BPB.md
| ... | ... | @@ -19,7 +19,7 @@ timeline |
| 19 | 19 | |
| 20 | 20 | |Entity|Tier|Description | |
| 21 | 21 | |:------:|:----:|--------------------------------------| |
| 22 | -| |2 |relevance in FL not firmly established[@hubschmannMutationalMechanismsShaping2021b]| |
|
| 22 | +| |2 |relevance in FL not firmly established[@hubschmannMutationalMechanismsShaping2021]| |
|
| 23 | 23 | |
| 24 | 24 | ||2|relevance in MZL not firmly established| |
| 25 | 25 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CDKN2A.md
| ... | ... | @@ -25,7 +25,7 @@ timeline |
| 25 | 25 | |Entity|Tier|Description | |
| 26 | 26 | |:------:|:----:|--------------------------------------| |
| 27 | 27 | ||1|high-confidence PMBL/cHL/GZL gene| |
| 28 | -||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016b]| |
|
| 28 | +||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016]| |
|
| 29 | 29 | | |1 |high-confidence DLBCL gene [@morinMutationalStructuralAnalysis2013]| |
| 30 | 30 | | |2 |relevance in BL not firmly established[@grandeGenomewideDiscoverySomatic2019]| |
| 31 | 31 |
CHD4.md
| ... | ... | @@ -17,7 +17,7 @@ timeline |
| 17 | 17 | |
| 18 | 18 | |Entity|Tier|Description | |
| 19 | 19 | |:------:|:----:|--------------------------------------| |
| 20 | -| |2 |relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022b]| |
|
| 20 | +| |2 |relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022]| |
|
| 21 | 21 | |
| 22 | 22 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 23 | 23 |
CIITA.md
| ... | ... | @@ -20,7 +20,7 @@ timeline |
| 20 | 20 | |
| 21 | 21 | |Entity|Tier|Description | |
| 22 | 22 | |:------:|:----:|--------------------------| |
| 23 | -||1|high-confidence PMBL/cHL/GZL gene[@mottokGenomicAlterationsCIITA2015b]| |
|
| 23 | +||1|high-confidence PMBL/cHL/GZL gene[@mottokGenomicAlterationsCIITA2015]| |
|
| 24 | 24 | | |1-a | aSHM target and high-confidence DLBCL gene[@morinFrequentMutationHistonemodifying2011]| |
| 25 | 25 | |
| 26 | 26 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CILP.md
| ... | ... | @@ -18,7 +18,7 @@ timeline |
| 18 | 18 | |
| 19 | 19 | |Entity|Tier|Description | |
| 20 | 20 | |:------:|:----:|--------------------------------------| |
| 21 | -| |2 |relevance in FL not firmly established[@russler-germainMutationsAssociatedProgression2023b]| |
|
| 21 | +| |2 |relevance in FL not firmly established[@russler-germainMutationsAssociatedProgression2023]| |
|
| 22 | 22 | |
| 23 | 23 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 24 | 24 |
CLGN.md
| ... | ... | @@ -20,7 +20,7 @@ timeline |
| 20 | 20 | |
| 21 | 21 | |Entity|Tier|Description| |
| 22 | 22 | |:------:|:----:|--------------------------------------| |
| 23 | -||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016b]| |
|
| 23 | +||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016]| |
|
| 24 | 24 | |
| 25 | 25 | |
| 26 | 26 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CNBP.md
| ... | ... | @@ -20,7 +20,7 @@ timeline |
| 20 | 20 | |
| 21 | 21 | |Entity|Tier|Description| |
| 22 | 22 | |:------:|:----:|--------------------------------------| |
| 23 | -||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016b]| |
|
| 23 | +||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016]| |
|
| 24 | 24 | |
| 25 | 25 | |
| 26 | 26 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CNKSR2.md
| ... | ... | @@ -20,7 +20,7 @@ timeline |
| 20 | 20 | |
| 21 | 21 | |Entity|Tier|Description| |
| 22 | 22 | |:------:|:----:|--------------------------------------| |
| 23 | -||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016b]| |
|
| 23 | +||2|relevance in MZL not firmly established[@spinaGeneticsNodalMarginal2016]| |
|
| 24 | 24 | |
| 25 | 25 | |
| 26 | 26 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CNOT2.md
| ... | ... | @@ -19,7 +19,7 @@ timeline |
| 19 | 19 | |
| 20 | 20 | |Entity|Tier|Description | |
| 21 | 21 | |:------:|:----:|-----------------------------------------| |
| 22 | -| |2 |relevance in DLBCL not firmly established[@hubschmannMutationalMechanismsShaping2021b]| |
|
| 22 | +| |2 |relevance in DLBCL not firmly established[@hubschmannMutationalMechanismsShaping2021]| |
|
| 23 | 23 | |
| 24 | 24 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 25 | 25 |
COQ7.md
| ... | ... | @@ -18,7 +18,7 @@ timeline |
| 18 | 18 | |
| 19 | 19 | |Entity|Tier|Description | |
| 20 | 20 | |:------:|:----:|-----------------------------------------| |
| 21 | -| |2 |relevance in DLBCL not firmly established[@chapuyMolecularSubtypesDiffuse2018b]| |
|
| 21 | +| |2 |relevance in DLBCL not firmly established[@chapuyMolecularSubtypesDiffuse2018]| |
|
| 22 | 22 | |
| 23 | 23 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 24 | 24 |
CPNE8.md
| ... | ... | @@ -19,7 +19,7 @@ timeline |
| 19 | 19 | |
| 20 | 20 | |Entity|Tier|Description | |
| 21 | 21 | |:------:|:----:|--------------------------------------| |
| 22 | -| |2 |relevance in FL not firmly established[@hubschmannMutationalMechanismsShaping2021b]| |
|
| 22 | +| |2 |relevance in FL not firmly established[@hubschmannMutationalMechanismsShaping2021]| |
|
| 23 | 23 | |
| 24 | 24 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 25 | 25 |
CPS1.md
| ... | ... | @@ -20,7 +20,7 @@ timeline |
| 20 | 20 | |
| 21 | 21 | |Entity|Tier|Description| |
| 22 | 22 | |:------:|:----:|--------------------------------------| |
| 23 | -||2|relevance in DLBCL not firmly established[@lohrDiscoveryPrioritizationSomatic2012a]| |
|
| 23 | +||2|relevance in DLBCL not firmly established[@lohrDiscoveryPrioritizationSomatic2012]| |
|
| 24 | 24 | |
| 25 | 25 | |
| 26 | 26 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CPXM2.md
| ... | ... | @@ -18,7 +18,7 @@ timeline |
| 18 | 18 | |
| 19 | 19 | |Entity|Tier|Description | |
| 20 | 20 | |:------:|:----:|--------------------------------------| |
| 21 | -| |2 |relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022b]| |
|
| 21 | +| |2 |relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022]| |
|
| 22 | 22 | |
| 23 | 23 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 24 | 24 |
CREBBP.md
| ... | ... | @@ -7,13 +7,13 @@ link-citations: true |
| 7 | 7 | # CREBBP |
| 8 | 8 | |
| 9 | 9 | ## Overview |
| 10 | -CREBBP mutations are highly prevalent in both DLBCL and FL.[@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
|
| 10 | +CREBBP mutations are highly prevalent in both DLBCL and FL.[@pasqualucciInactivatingMutationsAcetyltransferase2011] |
|
| 11 | 11 | 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] |
| 12 | 12 | |
| 13 | 13 | ## Experimental Evidence |
| 14 | -CREBBP missense mutations often affect the histone acetyltransferase (HAT) domain, crucial for regulating gene expression through chromatin modification, or generate a truncated protein.[@pasqualucciInactivatingMutationsAcetyltransferase2011a] |
|
| 14 | +CREBBP missense mutations often affect the histone acetyltransferase (HAT) domain, crucial for regulating gene expression through chromatin modification, or generate a truncated protein.[@pasqualucciInactivatingMutationsAcetyltransferase2011] |
|
| 15 | 15 | In a transgenic mouse model, CREBBP loss cooperated with BCL2 overexpression to promote B-cell lymphomagenesis.[@garcia-ramirezCrebbpLossCooperates2017] |
| 16 | -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] |
|
| 16 | +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.[@nieGenomewideCRISPRScreens2021] |
|
| 17 | 17 | |
| 18 | 18 | ## History |
| 19 | 19 |
CRIP1.md
| ... | ... | @@ -18,7 +18,7 @@ timeline |
| 18 | 18 | |
| 19 | 19 | |Entity|Tier|Description | |
| 20 | 20 | |:------:|:----:|-----------------------------------------| |
| 21 | -| |2 |relevance in DLBCL not firmly established[@chapuyMolecularSubtypesDiffuse2018b]| |
|
| 21 | +| |2 |relevance in DLBCL not firmly established[@chapuyMolecularSubtypesDiffuse2018]| |
|
| 22 | 22 | |
| 23 | 23 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 24 | 24 |
CSF2RB.md
| ... | ... | @@ -20,7 +20,7 @@ timeline |
| 20 | 20 | |
| 21 | 21 | |Entity|Tier|Description| |
| 22 | 22 | |:------:|:----:|--------------------------------------| |
| 23 | -||1|high-confidence PMBL/cHL/GZL gene[@reichelFlowSortingExome2015a]| |
|
| 23 | +||1|high-confidence PMBL/cHL/GZL gene[@reichelFlowSortingExome2015]| |
|
| 24 | 24 | |
| 25 | 25 | |
| 26 | 26 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
CTSS.md
| ... | ... | @@ -18,7 +18,7 @@ timeline |
| 18 | 18 | |
| 19 | 19 | |Entity|Tier|Description | |
| 20 | 20 | |:------:|:----:|-----------------------| |
| 21 | -| |1 |high-confidence FL gene[@barariaCathepsinAlterationsInduce2020c]| |
|
| 21 | +| |1 |high-confidence FL gene[@barariaCathepsinAlterationsInduce2020]| |
|
| 22 | 22 | |
| 23 | 23 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 24 | 24 |
CXCR4.md
| ... | ... | @@ -10,7 +10,7 @@ link-citations: true |
| 10 | 10 | CXCR4 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. No notable hot spots have been described in this gene in the context of the cancers listed below. The mutation pattern in DLBCL implies the preferential accumulation of *inactivating mutations*. |
| 11 | 11 | |
| 12 | 12 | ## History |
| 13 | -Mutations in this gene were first described in DLBCL in 2012 by Khodabakhshi et al,<sup>1</sup> in FL in 2021 by Hübschmann et al<sup>2</sup> and in BL in 2019 by Panea et al.<sup>3</sup> |
|
| 13 | +Mutations in this gene were first described in DLBCL in 2012 [@khodabakhshiRecurrentTargetsAberrant2012] in FL in 2021 [@hubschmannMutationalMechanismsShaping2021] and in BL in 2019.[@paneaWholeGenomeLandscape2019] |
|
| 14 | 14 | |
| 15 | 15 | |
| 16 | 16 | ```mermaid |
| ... | ... | @@ -31,7 +31,7 @@ timeline |
| 31 | 31 | |:------:|:----:|--------------------------------------| |
| 32 | 32 | ||1|high-confidence MZL gene| |
| 33 | 33 | | |1 | aSHM target and high-confidence DLBCL gene [@khodabakhshiRecurrentTargetsAberrant2012]| |
| 34 | -| |2 | aSHM target; Although recurrent, the relevance of mutations in FL is tenuous [@krysiakRecurrentSomaticMutations2017b]| |
|
| 34 | +| |2 | aSHM target; Although recurrent, the relevance of mutations in FL is tenuous [@krysiakRecurrentSomaticMutations2017]| |
|
| 35 | 35 | | |2 | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@paneaWholeGenomeLandscape2019]| |
| 36 | 36 | |
| 37 | 37 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |