Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities
Ho S, Sheng T, Xing M, Ooi W, Xu C, Sundar R, Huang K, Li Z, Kumar V, Ramnarayanan K, Zhu F, Srivastava S, Bin Adam Isa Z, Anene-Nzelu C, Razavi-Mohseni M, Shigaki D, Ma H, Tan A, Ong X, Lee M, Tay S, Guo Y, Huang W, Li S, Beer M, Foo R, Teh M, Skanderup A, Teh B, Tan P. Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities. Gut 2022, 72: 226-241. PMID: 35817555, DOI: 10.1136/gutjnl-2021-326483.Peer-Reviewed Original ResearchConceptsEpigenomic landscapeGastric cancerEnhancer landscapeGenome-wide epigenomic profilesDownstream targetsPharmacological inhibitionCell linesClinically aggressive subtypeTargetable genomic alterationsMultiple molecular subtypesChIP-seqPoor patient survivalGenomic associationsGC cell linesTranscriptomic scenarioEpigenomic profilingSuper-enhancersChromatin immunoprecipitationRNA sequencingTranscriptome profilingUpstream regulatorGenomic alterationsTherapy resistanceCRISPR/Cas9 editingPatient survivalChromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer.
Nargund A, Xu C, Mandoli A, Okabe A, Chen G, Huang K, Sheng T, Yao X, Teo J, Sundar R, Kok Y, See Y, Xing M, Li Z, Yong C, Anand A, Bin Adam Isa Z, Poon L, Ng M, Koh J, Ooi W, Tay S, Ong X, Tan A, Smoot D, Ashktorab H, Grabsch H, Fullwood M, Teh B, Bi X, Kaneda A, Li S, Tan P. Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer. Cancer Research 2022, 82: 2538-2551. PMID: 35583999, DOI: 10.1158/0008-5472.can-21-2072.Peer-Reviewed Original ResearchConceptsEnhancer-promoter interactionsCell adhesion genesGenomic bindingAdhesion genesExpression of cell adhesion genesPathway expressionBET inhibitionCell adhesion pathwaysFunction of MSH2DNA mismatch repair genes MSH2Mismatch repair genes MSH2Sensitivity to BET inhibitionTumorigenesis in vitroHistone acetylation levelsChromatin rewiringChromatin functionEpigenomic functionsDNA repair genesSuper-enhancersGene locusEpigenomic regulationFunctional screeningSynthetic lethalityDNA repairAdhesion pathways