Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration
2019
Hye-Jung E. Chun | Pascal D. Johann | Katy Milne | Marc Zapatka | Annette Buellesbach | Naveed Ishaque | Murat Iskar | Serap Erkek | Lisa Wei | Basile Tessier-Cloutier | Jake Lever | Emma Titmuss | James T. Topham | Reanne Bowlby | Eric Chuah | Karen L. Mungall | Yussanne Ma | Andrew J. Mungall | Richard A. Moore | Michael D. Taylor | Daniela S. Gerhard | Steven J.M. Jones | Andrey Korshunov | Manfred Gessler | Kornelius Kerl | Martin Hasselblatt | Michael C. Frühwald | Elizabeth J. Perlman | Brad H. Nelson | Stefan M. Pfister | Marco A. Marra | Marcel Kool
Summary: Extra-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. : Chun et al. report similarities between the MYC subgroup of cranial and extra-cranial rhabdoid tumors (RTs) at genetic, gene-expression, and epigenetic levels. They identify five DNA methylation subgroups of RTs across multiple organ sites, and some subgroups exhibit increased levels of immune cell infiltration and immune checkpoint expression. Keywords: Malignant rhabdoid tumor, atypical teratoid rhabdoid tumor, pediatric cancer, SMARCB1, molecular subgroups, genomic and epigenomic dysregulation, HOX dysregulation, cytotoxic T cell infiltration, tumor-infiltrating immune cells
Show more [+] Less [-]Bibliographic information
This bibliographic record has been provided by Directory of Open Access Journals