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

Child DNA Methylation / genetics Female Humans Lymphocytes, Tumor-Infiltrating / metabolism Male Mutation / genetics Rhabdoid Tumor / metabolism SMARCB1 Protein / genetics Skull Base Neoplasms / metabolism T-Lymphocytes / metabolism T-Lymphocytes, Cytotoxic / metabolism Teratoma / metabolism
HOX dysregulation Malignant rhabdoid tumor SMARCB1 atypical teratoid rhabdoid tumor cytotoxic T cell infiltration genomic and epigenomic dysregulation molecular subgroups pediatric cancer tumor-infiltrating immune cells

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
19 11 2019
Historique:
received: 18 01 2019
revised: 20 08 2019
accepted: 02 10 2019
pubmed: 12 11 2019
medline: 22 9 2020
entrez: 12 11 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2019.10.013 PMID: 31708418 PMC: PMC6905433
pubmed: 31708418
pii: S2211-1247(19)31313-0
doi: 10.1016/j.celrep.2019.10.013
pmc: PMC6905433
mid: NIHMS1544232
pii:
doi:

Substances chimiques

SMARCB1 Protein 0
SMARCB1 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2338-2354.e7

Subventions

Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Hye-Jung E Chun (HE)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Pascal D Johann (PD)

Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany.

Katy Milne (K)

Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.

Marc Zapatka (M)

Department of Molecular Genetics, DKFZ, Heidelberg 69120, Germany.

Annette Buellesbach (A)

Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany.

Naveed Ishaque (N)

Center for Digital Health, Berlin Institute of Health and Charité-Universitätsmedizin Berlin, Berlin 10117, Germany; Heidelberg Center for Personalized Oncology, DKFZ, Heidelberg 69120, Germany.

Murat Iskar (M)

Department of Molecular Genetics, DKFZ, Heidelberg 69120, Germany.

Serap Erkek (S)

Hopp Children's Cancer Center, Heidelberg 69120, Germany.

Lisa Wei (L)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Basile Tessier-Cloutier (B)

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6H 3N1, Canada.

Jake Lever (J)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Emma Titmuss (E)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

James T Topham (JT)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Reanne Bowlby (R)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Eric Chuah (E)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Karen L Mungall (KL)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Yussanne Ma (Y)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Andrew J Mungall (AJ)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Richard A Moore (RA)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.

Michael D Taylor (MD)

Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

Daniela S Gerhard (DS)

Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Steven J M Jones (SJM)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.

Andrey Korshunov (A)

Hopp Children's Cancer Center, Heidelberg 69120, Germany.

Manfred Gessler (M)

Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry; and Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg 97074, Germany.

Kornelius Kerl (K)

Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster 48149, Germany.

Martin Hasselblatt (M)

Institute of Neuropathology, University Hospital Muenster, Muenster 48149, Germany.

Michael C Frühwald (MC)

University Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg 86156, Germany.

Elizabeth J Perlman (EJ)

Department of Pathology and Laboratory Medicine, Lurie Children's Hospital, Northwestern University's Feinberg School of Medicine and Robert H. Lurie Cancer Center, Chicago, IL 60611, USA.

Brad H Nelson (BH)

Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 3E6, Canada.

Stefan M Pfister (SM)

Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany.

Marco A Marra (MA)

Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada. Electronic address: mmarra@bcgsc.ca.

Marcel Kool (M)

Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany. Electronic address: m.kool@kitz-heidelberg.de.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes TIL › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs complexes et mixtes › Tumeur rhabdoïde › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéine SMARCB1 › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Maladies ostéomusculaires › Maladies osseuses › Tumeurs osseuses › Tumeurs du crâne › Tumeurs de la base du crâne › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T cytotoxiques › Identification and Analyses of Extra-Cranial...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs embryonnaires et germinales › Tératome › Identification and Analyses of Extra-Cranial...