Jonathon TorchiaBrian GolbournShengrui FengKing Ching HoPatrick Sin-ChanAlexandre VasiljevicJoseph D. NormanPaul GuilhamonLivia GarziaNatalia R. AgamezMei LuTiffany S. ChanDaniel PicardPasqualino de AntonellisDong Anh Khuong-QuangAline C. PlanelloConstanze ZellerDalia Barsyte-LovejoyLucie Lafay-CousinLouis LetourneauMathieu BourgeyMan YuDeena M.A. GendooMisko DzambaMark BarszczykTiago MedinaAlexandra N. RiemenschneiderA. Sorana MorrissyYoung Shin RaVijay RamaswamyMarc RemkeChristopher P. DunhamStephen YipHo keung NgJian Qiang LuVivek MehtaSteffen AlbrechtJose PimentelJennifer A. ChanGino R. SomersClaudia C. FariaLucia RoqueMaryam FouladiLindsey M. HoffmanAndrew S. MooreYin WangSeung Ah ChoiJordan R. HansfordDaniel CatchpooleDiane K. BirksNicholas K. ForemanDoug StrotherAlmos KleknerLaszló BognárMiklós GaramiPéter HauserTibor HortobágyiBeverly WilsonJuliette HukinAnne Sophie CarretTimothy E. Van MeterEugene I. HwangAmar GajjarShih Hwa ChiouHideo NakamuraHelen ToledanoIris FriedDaniel FultsTakafumi WatayaChris FryerDavid D. EisenstatKatrin ScheinemannAdam J. FlemingDonna L. JohnstonJean MichaudUniversity of TorontoHospital for Sick Children University of TorontoOntario Cancer Institute University of TorontoCHU de LyonMcGill UniversityAlberta Children's HospitalUniversity of CalgaryAsan Medical CenterThe University of British ColumbiaChinese University of Hong KongUniversity of AlbertaSanta Maria Hospital, LisbonInstituto Portugues de Oncologia de Francisco Gentil LisboaCincinnati Children's Hospital Medical CenterUniversity of Colorado School of MedicineUniversity of QueenslandFudan UniversitySeoul National University College of MedicineRoyal Children's Hospital, MelbourneChildren's Hospital At WestmeadDebreceni Egyetem Altalanos Orvostudomanyi KarSemmelweis EgyetemSzegedi Tudomanyegyetem (SZTE)University of MontrealVirginia Commonwealth UniversityChildrens National Health SystemSt. Jude Children's Research HospitalNational Yang-Ming University TaiwanKumamoto UniversityChildren's Medical Center of IsraelHadassah University Medical CentreUniversity of Utah, School of MedicineShizuoka Children's HospitalMcMaster University, Faculty of Health SciencesChildren's Hospital of Eastern Ontario, OttawaLondon Health Sciences CentreWestern UniversityDalhousie UniversityMahidol UniversityUniversity of NottinghamAnn & Robert H. Lurie Children's Hospital of ChicagoUniversity of California, San FranciscoUniversity of AlabamaJulius-Maximilians-Universität Würzburg2018-12-112019-03-142018-12-112019-03-142016-12-12Cancer Cell. Vol.30, No.6 (2016), 891-90818783686153561082-s2.0-85004009880https://repository.li.mahidol.ac.th/handle/20.500.14594/42259© 2016 Elsevier Inc. We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1016/j.ccell.2016.11.003