2022
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 ResearchMeSH KeywordsCisplatinEnhancer Elements, GeneticEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansProspective StudiesProtein KinasesRepressor ProteinsRetrospective StudiesStomach NeoplasmsConceptsEpigenomic 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 survival
2021
Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer
Sheng T, Ho S, Ooi W, Xu C, Xing M, Padmanabhan N, Huang K, Ma L, Ray M, Guo Y, Sim N, Anene-Nzelu C, Chang M, Razavi-Mohseni M, Beer M, Foo R, Sundar R, Chan Y, Tan A, Ong X, Skanderup A, White K, Jha S, Tan P. Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer. Genome Medicine 2021, 13: 158. PMID: 34635154, PMCID: PMC8504099, DOI: 10.1186/s13073-021-00970-3.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationADP-Ribosylation FactorsCell Line, TumorCell ProliferationChromatinEnhancer Elements, GeneticEpigenomicsGene Expression Regulation, NeoplasticGenomicsHistonesHumansInhibitor of Growth Protein 1OncogenesPromoter Regions, GeneticRNA-SeqStomach NeoplasmsTranscriptomeWhole Genome SequencingConceptsSingle nucleotide polymorphismsActivity-by-contactEnhancer-promoter interactionsSomatic copy number alterationsGermline single nucleotide polymorphismsHistone modificationsDistal cis-regulatory elementsLow somatic mutation rateCell-specific gene expressionCis-regulatory elementsFunctional enhancer activityHistone modification profilesWhole-genome sequencingRegulatory region sequencingCell fate determinationSuper-enhancer regionsCopy number alterationsGenome copy numberEffect of histone acetylationSomatic mutation rateCancer-relevant genesFunctional assay dataEnhanced activityGC cell linesRegion sequences“3G” Trial: An RNA Editing Signature to Guide Gastric Cancer ChemotherapyRNA Editing Signature in Gastric Cancer
An O, Song Y, Ke X, So J, Sundar R, Yang H, Rha S, Lee M, Tay S, Ong X, Tan A, Ng M, Tantoso E, Chen L, Tan P, Yong W, Consortium S. “3G” Trial: An RNA Editing Signature to Guide Gastric Cancer ChemotherapyRNA Editing Signature in Gastric Cancer. Cancer Research 2021, 81: 2788-2798. PMID: 33558338, DOI: 10.1158/0008-5472.can-20-2872.Peer-Reviewed Original ResearchConceptsAdvanced gastric cancerRNA editingRNA editing signaturesEditing levelsGastric cancerRNA editing eventsHigher editing levelsAdenosine-to-inosineRNA editing analysisGastric cancer cell linesPredictive biomarkersStratify patientsLevels of editingGene expression profilesPredicting response to chemotherapyEditing sitesEditing eventsMolecular subtypes of gastric cancerCancer cell linesPlatinum-based chemotherapyMetastatic gastric cancerSubtypes of gastric cancerCancer Genome AtlasFirst-line therapyResponse to chemotherapy
2018
Transcriptional analysis of immune genes in Epstein–Barr virus-associated gastric cancer and association with clinical outcomes
Sundar R, Qamra A, Tan A, Zhang S, Ng C, Teh B, Lee J, Kim K, Tan P. Transcriptional analysis of immune genes in Epstein–Barr virus-associated gastric cancer and association with clinical outcomes. Gastric Cancer 2018, 21: 1064-1070. PMID: 29915957, DOI: 10.1007/s10120-018-0851-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedB7-H1 AntigenBiomarkers, TumorCD8 AntigensCohort StudiesDisease-Free SurvivalEpstein-Barr Virus InfectionsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHerpesvirus 4, HumanHumansImmunohistochemistryLymphocytes, Tumor-InfiltratingMaleMiddle AgedPerforinProgrammed Cell Death 1 ReceptorStomach NeoplasmsConceptsPD-L1PD-L1highPD-L1lowEBVaGC samplesImmune-related genesAssociated with worse disease-free survivalGastric cancerPD-L1 immunohistochemistry expressionPD-L1 transcript expressionExpression of PD-L1Levels of PD-L1Epstein-Barr virus-associated gastric cancerTumour-infiltrating lymphocyte patternPD-L1 expressionPD-L1 immunohistochemistryPrimary tumor resectionDisease-free survivalAssociated with higher expressionCases of EBVaGCGastric cancer patientsEBV-negative samplesSamsung Medical CentreAsian Cancer Research GroupImmune genesCancer Research GroupAtaxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer
Sundar R, Miranda S, Rodrigues D, Chénard-Poirier M, Dolling D, Clarke M, Figueiredo I, Bertan C, Yuan W, Ferreira A, Chistova R, Boysen G, Perez D, Tunariu N, Mateo J, Wotherspoon A, Chau I, Cunningham D, Valeri N, Carreira S, de Bono J. Ataxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer. Clinical Colorectal Cancer 2018, 17: 280-284. PMID: 30042009, DOI: 10.1016/j.clcc.2018.05.011.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsBiomarkers, TumorColorectal NeoplasmsDNA RepairFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansLiver NeoplasmsMaleMiddle AgedOxaliplatinPrognosisRetrospective StudiesSurvival RateYoung AdultConceptsATM lossColorectal cancerAssociated with superior overall survivalDNA repair targeting agentsMetastatic colorectal cancer patientsAtaxia telangiectasiaIrinotecan-based therapySuperior overall survivalOxaliplatin-based therapyOxaliplatin-based chemotherapyTreatment of colorectal cancerATM protein expressionClinical outcome dataNuclear staining intensityColorectal cancer patientsDrug Development UnitColorectal cancer samplesOverall survivalMutation statusH-scoreTargeted agentsClinical outcomesDNA repair signalingTumor samplesCancer patients