Department of Pathology, St Jude Children’s Research Hospital, Memphis, TN, USAPetri Pölönen, Danika Di Giacomo, Abdelrahman Elsayed, Shunsuke Kimura, Francesca Benini, Lindsey E. Montefiori, Ilaria Iacobucci, Yunchao Chang, Yaqi Zhao, Pankaj S. Ghate & Charles G. MullighanDepartment of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, ItalyDanika Di GiacomoDepartment of Biostatistics, St Jude Children’s Research Hospital, Memphis, TN, USAAnna Eames Seffernick, Abdelrahman Elsayed & Stanley B. PoundsDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyFrancesca BeniniDepartment of Pediatric Hematology and Oncology, Bambino Gesù Children’s Research Hospital, Rome, ItalyFrancesca BeniniChildren’s Hospital Los Angeles, Laboratory Medicine, Los Angeles, CA, USABrent L. WoodPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAJason Xu, Jonathan Sussman, Caroline Diorio, David Frank, Kathrin M. Bernt, Stephen P. Hunger, Kai Tan & David T. TeacheyDivision of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA, USAChangya Chen, Elizabeth Li, Caroline Diorio, Lahari Uppuluri, Alexander Li, Kathrin M. Bernt, Tiffaney L. Vincent, Stephen P. Hunger, Kai Tan & David T. TeacheyDepartment of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, USAChangya ChenCenter for Applied Bioinformatics, St Jude Children’s Research Hospital, Memphis, TN, USAZhongshan Cheng, Jason Myers, Dale Hedges, Yawei Hui, Yiping Fan, Evadnie Rampersaud, Ti-Cheng Chang & Gang WuDepartment of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA, USAHaley Newman, Caroline Diorio, Rawan Shraim, Kathrin M. Bernt, Stephen P. Hunger & David T. TeacheyFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USASoheil Meshinchi & Rhonda RiesGlobal Pediatric Medicine, St Jude Children’s Research Hospital, Memphis, TN, USAMeenakshi DevidasResearch Institute and Cancer and Blood Disorders Program, Children’s Minnesota, Minneapolis, MN, USAStuart S. WinterDivision of Oncology, University of Virginia Children’s Hospital, Charlottesville, VA, USAKimberly P. DunsmoreDepartment of Oncology, St Jude Children’s Research Hospital, Memphis, TN, USAHiroto InabaDivision of Pediatric Hematology Oncology, Department of Pediatrics, NYU Langone Health, New York, NY, USAWilliam L. Carroll & Elizabeth RaetzDepartment of Pediatrics and Pathology, Perlmutter Cancer Center, NYU Langone Health, New York, NY, USAWilliam L. Carroll & Elizabeth RaetzDepartment of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, USANilsa C. RamirezDepartment of Structural Biology, St Jude Children’s Research Hospital, Memphis, TN, USAAaron H. Phillips & Richard W. KriwackiDepartment of Microbiology, Immunology and Biochemistry, University of Tennessee Health Sciences Center, Memphis, TN, USARichard W. KriwackiDepartment of Pharmaceutical Sciences, St Jude Children’s Research Hospital, Memphis, TN, USAJun J. YangDepartment of Computational Biology, St Jude Children’s Research Hospital, Memphis, TN, USAJian Wang, Colleen Reilly & Xin ZhouDepartment of Hematology, Erasmus MC Cancer Institute, Rotterdam, The NetherlandsMathijs A. SandersCancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UKMathijs A. SandersDepartment of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto, JapanJunko TakitaDepartment of Pediatrics, Tokyo University, Tokyo, JapanMotohiro Kato & Nao TakasugiDepartment of Pediatrics, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USABill H. ChangDepartment of Pathology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USARichard D. PressDepartment of Pediatrics and the Ben Towne Center for Childhood Cancer Research, Seattle Children’s Hospital, University of Washington, Seattle, WA, USAMignon LohCenter for Single Cell Biology, Children’s Hospital of Philadelphia, Philadelphia, PA, USAKai TanM.L., E. Raetz, S.P.H., J.J.Y., M.D., H.I., S.W., K.D., W.L.C., N.C.R., K.B., C.D., L.U., D.F., S.M., R.R., A.L., T.L.V., P.S.G., M.A.S., J.T., M.K., N.T., B.H.C., R.D.P. and Y.Z. provided patient samples and collected data. P.P., Z.C., J.M., Y.H., Y.F., D.H. and E. Rampersaud preprocessed data. P.P., T.-C.C., G.W., H.N. and R.S. analysed genomic data. P.P., A.E.S., A.E. and S.B.P. performed statistical analyses. P.P., J.X., C.C., E.L., J.S., A.L. and K.T. analysed scRNA data. P.P., J.W., C.R. and X.Z. generated cloud-based visualizations. R.R., S.M. and T.V. isolated DNA and RNA. J.X. and C.C. performed single cell library preparation and sequencing. D.D.G. and L.E.M. performed HiChIP and ATAC–seq. R.D.P. performed targeted amplicon sequencing. F.B. and S.K. performed long-read sequencing. S.K. engineered MED12 KO cells, Y.C. performed western blotting. F.B., I.I. and S.K. performed luciferase report assays. B.L.W. analysed flow cytometry data. A.H.P. and R.W.K. analyzed AlphaFold2 models. P.P., C.G.M. and D.T.T. designed the study and wrote the manuscript.
