2023
Comprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities
Xu C, Huang K, Law J, Chua J, Sheng T, Flores N, Pizzi M, Okabe A, Tan A, Zhu F, Kumar V, Lu X, Benitez A, Lian B, Ma H, Ho S, Ramnarayanan K, Anene-Nzelu C, Razavi-Mohseni M, Ghani S, Tay S, Ong X, Lee M, Guo Y, Ashktorab H, Smoot D, Li S, Skanderup A, Beer M, Foo R, Wong J, Sanghvi K, Yong W, Sundar R, Kaneda A, Prabhakar S, Mazur P, Ajani J, Yeoh K, So J, Tan P. Comprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities. Gut 2023, 72: 1651-1663. PMID: 36918265, DOI: 10.1136/gutjnl-2022-328332.Peer-Reviewed Original ResearchConceptsGastric cancerMolecular subtypesPromoter activityMutational signaturesProinflammatory tumor microenvironmentTumor microenvironmental changesMutated driver genesSingle-cell transcriptome profilingCTCF occupancyGC molecular subtypesChromatin profilingDistal enhancerRegulatory networksEpigenetic landscapeBRD4 bindingEpigenomic reprogrammingEpigenomic levelsTumor-intrinsicTumor inflammationTumor microenvironmentTherapeutic vulnerabilitiesTranscriptome profilingDriver genesNFkB inhibitorGene expression
2022
Chromatin 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
2018
Clinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials
Sundar R, McVeigh T, Dolling D, Petruckevitch A, Diamantis N, Ang J, Chenard-Poiriér M, Collins D, Lim J, Ameratunga M, Khan K, Kaye S, Banerji U, Lopez J, George A, de Bono J, van der Graaf W. Clinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials. European Journal Of Cancer 2018, 101: 55-61. PMID: 30025230, DOI: 10.1016/j.ejca.2018.06.003.Peer-Reviewed Original ResearchConceptsPhase I trialPhase I clinical trialAdvanced solid tumorsI trialOverall survivalAYA patientsSolid tumorsCancer syndromesCohort of AYA patientsMolecular characterisation of tumoursOutcomes of AYA patientsClinical benefit rateMedian overall survivalOutcomes of AYAsSomatic genetic aberrationsSignificant family historyRoyal Marsden HospitalHereditary cancer syndromesCharacterisation of tumoursTherapeutic treatment optionsClinical outcomes of adolescentsClinical trial dataDrug Development UnitYoung adultsGenetic aberrations