ArticleNature genetics2014
Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR.
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Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117 citing papers in PubMed, 198 citations in OpenAlex.
- Recurrent C19MC-altered embryonal tumors with multilayered rosettes: outcomes of stereotactic radiosurgery.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
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- Patient-derived pediatric brain tumor orthotopic xenografts and tumor organoids faithfully recapitulate primary tumors.Science advances · 2026Article
- Freiburg Neuropathology Case Conference: A 2-Year-Old Child with Progressive Headache, Nausea, and Personality Change.Clinical neuroradiology · 2026Article
- YAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class "embryonal tumor with multilayered rosettes, non-C19MC-altered" in the Heidelberg central nervous system tumor classifier and "embryonal tumor with multilayered rosettes-DICER" in the NIH classifier.Acta neuropathologica communications · 2025Article
- In vivo intratumoral heterogeneity in a dish: scalable forebrain organoid models of embryonal brain tumors for high-throughput personalized drug discovery.Cancer communications (London, England) · 2025Article
- CEBPB, C19MC, and Defective Autophagy Drive Novel Podosomal Belt to Macropinocytosis Transition, Lipid Accumulation, and HBV A-to-I RNA-editing.Research square · 2025Article
- The Chromosome 19 microRNA Cluster Facilitates Cancer Stemness in Hepatocellular Carcinoma.Non-coding RNA · 2025Article
- ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.Nature communications · 2025Article
- Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.Nature cancer · 2025Article
- Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review).Molecular and clinical oncology · 2025Review
- Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation.Frontiers in oncology · 2025Review
- Review
- Article
- Expression study of microRNA cluster on chromosome 19 (C19MC) in tumor tissue and serum of breast cancer patient.Molecular biology reports · 2023Article
- Methylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains.Experimental neurobiology · 2023Article
- SFyNCS detects oncogenic fusions involving non-coding sequences in cancer.Nucleic acids research · 2023Article
- Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer.Functional & integrative genomics · 2023Article
- OpenPBTA: The Open Pediatric Brain Tumor Atlas.Cell genomics · 2023Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
42 authors at 11 institutions in 3 countries.
Claudia L Kleinman1] McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [3].
Noha Gerges1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [2].
Simon Papillon-CavanaghMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Patrick Sin-ChanDivision of Hematology-Oncology, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Albena PramatarovaMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Dong-Anh Khuong QuangDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Véronique AdoueMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Stephan BuscheMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Maxime CaronMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Haig DjambazianMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Amandine BemmoMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Adam M FontebassoDivision of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Tara SpenceDivision of Hematology-Oncology, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jeremy SchwartzentruberMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Steffen AlbrechtDepartment of Pathology, McGill University Health Centre, Montreal, Quebec, Canada.
Peter HauserSecond Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Miklos GaramiSecond Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Almos KleknerDepartment of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Laszlo BognarDepartment of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Jose-Luis MontesDivision of Neurosurgery, Department of Surgery, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Alfredo StaffaMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Alexandre MontpetitMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Pierre BerubeMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Magdalena ZakrzewskaDepartment of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Krzysztof ZakrzewskiDepartment of Neurosurgery, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Pawel P LiberskiDepartment of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Zhifeng DongRosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
Peter M SiegelRosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
Thomas DuchaineDepartment of Biochemistry, McGill University, Montreal, Quebec, Canada.
Christian PerottiDepartment of Pathology & Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
Adam FlemingDivision of Pediatric Hematology-Oncology, Department of Pediatrics, McGill University and the McGill University Health Centre Research Institute, Montreal, Quebec, Canada.
Damien FauryDivision of Pediatric Hematology-Oncology, Department of Pediatrics, McGill University and the McGill University Health Centre Research Institute, Montreal, Quebec, Canada.
Marc RemkeDivision of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Marco GalloDivision of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Peter DirksDivision of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Michael D TaylorDivision of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Robert Sladek1] McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Tomi PastinenMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
Jennifer A ChanDepartment of Pathology & Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
Annie Huang1] Division of Hematology-Oncology, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Program in Cell Biology, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. [3].
Jacek Majewski1] McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [3].
Nada Jabado1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [2] Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada. [3].
McGill University and Génome Québec Innovation Centre · CAMcGill University Health Centre · CAHospital for Sick Children · CAMcGill University · CAMedical University of Lodz · PLSemmelweis University · HUSickKids Foundation · CAUniversity of Calgary · CAUniversity of Debrecen · HUMontreal Children's Hospital · CAPolish Mother’s Memorial Hospital Research Institute · PL
Funding
Canadian Institutes of Health Research 102684
Abstract
Embryonal tumors with multilayered rosettes (ETMRs) are rare, deadly pediatric brain tumors characterized by high-level amplification of the microRNA cluster C19MC. We performed integrated genetic and epigenetic analyses of 12 ETMR samples and identified, in all cases, C19MC fusions to TTYH1 driving expression of the microRNAs. ETMR tumors, cell lines and xenografts showed a specific DNA methylation pattern distinct from those of other tumors and normal tissues. We detected extreme overexpression of a previously uncharacterized isoform of DNMT3B originating at an alternative promoter that is active only in the first weeks of neural tube development. Transcriptional and immunohistochemical analyses suggest that C19MC-dependent DNMT3B deregulation is mediated by RBL2, a known repressor of DNMT3B. Transfection with individual C19MC microRNAs resulted in DNMT3B upregulation and RBL2 downregulation in cultured cells. Our data suggest a potential oncogenic re-engagement of an early developmental program in ETMR via epigenetic alteration mediated by an embryonic, brain-specific DNMT3B isoform.
Indexed as
Chromosomes, Human, Pair 19Brain NeoplasmsChild, PreschoolDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3BGene Expression Regulation, NeoplasticGene FusionHumansMaleMembrane ProteinsMicroRNAsNeoplasms, Germ Cell and EmbryonalProtein IsoformsRetinoblastoma-Like Protein p130Xenograft Model Antitumor AssaysDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BMembrane ProteinsMicroRNAsProtein IsoformsRBL2 protein, humanRetinoblastoma-Like Protein p130TTYH1 protein, human
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