Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration

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dc.contributor.authorChun, Hye-Jung E.
dc.contributor.authorJohann, Pascal D.
dc.contributor.authorMilne, Katy
dc.contributor.authorZapatka, Marc
dc.contributor.authorBuellesbach, Annette
dc.contributor.authorIshaque, Naveed
dc.contributor.authorIskar, Murat
dc.contributor.authorErkek, Serap
dc.contributor.authorWei, Lisa
dc.contributor.authorTessier-Cloutier, Basile
dc.contributor.authorLever, Jake
dc.contributor.authorTitmuss, Emma
dc.contributor.authorTopham, James T.
dc.contributor.authorBowlby, Reanne
dc.contributor.authorChuah, Eric
dc.contributor.authorMungall, Karen L.
dc.contributor.authorMa, Yussanne
dc.contributor.authorMungall, Andrew J.
dc.contributor.authorMoore, Richard A.
dc.contributor.authorTaylor, Michael D.
dc.contributor.authorGerhard, Daniela S.
dc.contributor.authorJones, Steven J.M.
dc.contributor.authorKorshunov, Andrey
dc.contributor.authorGessler, Manfred
dc.contributor.authorKerl, Kornelius
dc.contributor.authorHasselblatt, Martin
dc.contributor.authorFruhwald, Michael C.
dc.contributor.authorPerlman, Elizabeth J.
dc.contributor.authorNelson, Brad H.
dc.contributor.authorPfister, Stefan M.
dc.contributor.authorMarra, Marco A.
dc.contributor.authorKool, Marcel
dc.date.accessioned2020-02-14T00:58:27Z
dc.date.available2020-02-14T00:58:27Z
dc.date.copyright2019en_US
dc.date.issued2019
dc.description.abstractExtra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are heterogeneous pediatric cancers driven primarily by SMARCB1 loss. To understand the genome-wide molecular relationships between MRTs and ATRTs, we analyze multi-omics data from 140 MRTs and 161 ATRTs. We detect similarities between the MYC subgroup of ATRTs (ATRT-MYC) and extra-cranial MRTs, including global DNA hypomethylation and overexpression of HOX genes and genes involved in mesenchymal development, distinguishing them from other ATRT subgroups that express neural-like features. We identify five DNA methylation subgroups associated with anatomical sites and SMARCB1 mutation patterns. Groups 1, 3, and 4 exhibit cytotoxic T cell infiltration and expression of immune checkpoint regulators, consistent with a potential role for immunotherapy in rhabdoid tumor patients.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipK.M. and B.H.N. thank the BC Cancer Foundation, the Canada Foundation for Innovation (CFI), Canada’s Networks of Centres of Excellence (BioCanRx), and Genome BC. M.A.M. gratefully acknowledges BC Cancer, the BC Cancer Foundation, the CFI, the Canada Research Chairs program, and the Canadian Institutes of Health Research (FDN-143288). H.-J.E.C. thanks the University of British Columbia for financial support through the Roman M. Babicki Fellowship in Medical Research. P.D.J. and M.K. gratefully acknowledge the Heidelberg School of Oncology and the Deutsche Forschungsgemeinschaft (DFG) (JO 1598/1-1) for funding and the EURHAB registry for providing samples. M.H. is supported by IZKF Münster (Ha3/019/15) and DFG (HA3060/5-1). M.C.F. is supported by the Deutsche Kinderkrebsstiftung. This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E.en_US
dc.identifier.citationChun, H.E., Johann, P.D., Milne, K., Zapatka, M., Buellesbach, A.,Ishaque, N., … Kool, M. (2019). Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration. Cell Reports, 29(8), 2338-2354.e7. https://doi.org/10.1016/j.celrep.2019.10.013en_US
dc.identifier.urihttps://doi.org/10.1016/j.celrep.2019.10.013
dc.identifier.urihttp://hdl.handle.net/1828/11552
dc.language.isoenen_US
dc.publisherCell Reportsen_US
dc.subjectMalignant rhabdoid tumor
dc.subjectatypical teratoid rhabdoid tumor
dc.subjectpediatric cancer
dc.subjectSMARCB1
dc.subjectmolecular subgroups
dc.subjectgenomic and epigenomic dysregulation
dc.subjectHOX dysregulation
dc.subjectcytotoxic T cell infiltration
dc.subjecttumor-infiltrating immune cells
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleIdentification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltrationen_US
dc.typeArticleen_US

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