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

Chun, Hye-Jung E.Johann, Pascal D.Milne, KatyZapatka, MarcBuellesbach, AnnetteIshaque, NaveedIskar, MuratErkek, SerapWei, LisaTessier-Cloutier, BasileLever, JakeTitmuss, EmmaTopham, James T.Bowlby, ReanneChuah, EricMungall, Karen L.Ma, YussanneMungall, Andrew J.Moore, Richard A.Taylor, Michael D.Gerhard, Daniela S.Jones, Steven J.M.Korshunov, AndreyGessler, ManfredKerl, KorneliusHasselblatt, MartinFruhwald, Michael C.Perlman, Elizabeth J.Nelson, Brad H.Pfister, Stefan M.Marra, Marco A.Kool, Marcel2020-02-142020-02-1420192019Chun, 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.2019.10.013https://doi.org/10.1016/j.celrep.2019.10.013http://hdl.handle.net/1828/11552Extra-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.enMalignant rhabdoid tumoratypical teratoid rhabdoid tumorpediatric cancerSMARCB1molecular subgroupsgenomic and epigenomic dysregulationHOX dysregulationcytotoxic T cell infiltrationtumor-infiltrating immune cellsIdentification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell InfiltrationArticleDepartment of Biochemistry and Microbiology