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


ABSTRACT: 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.

SUBMITTER: Chun HE 

PROVIDER: S-EPMC6905433 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Chun Hye-Jung E HE   Johann Pascal D PD   Milne Katy K   Zapatka Marc M   Buellesbach Annette A   Ishaque Naveed N   Iskar Murat M   Erkek Serap S   Wei Lisa L   Tessier-Cloutier Basile B   Lever Jake J   Titmuss Emma E   Topham James T JT   Bowlby Reanne R   Chuah Eric E   Mungall Karen L KL   Ma Yussanne Y   Mungall Andrew J AJ   Moore Richard A RA   Taylor Michael D MD   Gerhard Daniela S DS   Jones Steven J M SJM   Korshunov Andrey A   Gessler Manfred M   Kerl Kornelius K   Hasselblatt Martin M   Frühwald Michael C MC   Perlman Elizabeth J EJ   Nelson Brad H BH   Pfister Stefan M SM   Marra Marco A MA   Kool Marcel M  

Cell reports 20191107 8


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  ...[more]

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