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K27M in canonical and noncanonical H3 variants occurs in distinct oligodendroglial cell lineages in brain midline gliomas.
Jessa, Selin; Mohammadnia, Abdulshakour; Harutyunyan, Ashot S; Hulswit, Maud; Varadharajan, Srinidhi; Lakkis, Hussein; Kabir, Nisha; Bashardanesh, Zahedeh; Hébert, Steven; Faury, Damien; Vladoiu, Maria C; Worme, Samantha; Coutelier, Marie; Krug, Brian; Faria Andrade, Augusto; Pathania, Manav; Bajic, Andrea; Weil, Alexander G; Ellezam, Benjamin; Atkinson, Jeffrey; Dudley, Roy W R; Farmer, Jean-Pierre; Perreault, Sebastien; Garcia, Benjamin A; Larouche, Valérie; Blanchette, Mathieu; Garzia, Livia; Bhaduri, Aparna; Ligon, Keith L; Bandopadhayay, Pratiti; Taylor, Michael D; Mack, Stephen C; Jabado, Nada; Kleinman, Claudia L.
Afiliação
  • Jessa S; Quantitative Life Sciences, McGill University, Montreal, Quebec, Canada.
  • Mohammadnia A; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
  • Harutyunyan AS; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Hulswit M; Department of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  • Varadharajan S; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Lakkis H; Brain Tumour Program, Children's Cancer Centre and Department of Paediatrics, Baylor College of Medicine, Houston, TX, USA.
  • Kabir N; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
  • Bashardanesh Z; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Hébert S; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Faury D; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
  • Vladoiu MC; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
  • Worme S; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Coutelier M; Department of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  • Krug B; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Faria Andrade A; Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Pathania M; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Bajic A; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
  • Weil AG; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.
  • Ellezam B; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
  • Atkinson J; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Dudley RWR; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Farmer JP; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Perreault S; Department of Oncology and The Milner Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
  • Garcia BA; CRUK Children's Brain Tumour Centre of Excellence, University of Cambridge, Cambridge, UK.
  • Larouche V; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Blanchette M; Department of Pediatric Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Quebec, Canada.
  • Garzia L; Department of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Quebec, Canada.
  • Bhaduri A; Department of Pediatric Surgery, Division of Neurosurgery, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.
  • Ligon KL; Department of Pediatric Surgery, Division of Neurosurgery, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.
  • Bandopadhayay P; Department of Pediatric Surgery, Division of Neurosurgery, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.
  • Taylor MD; Division of Child Neurology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec, Canada.
  • Mack SC; Department of Biochemistry and Biophysics and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Jabado N; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
  • Kleinman CL; Department of Pediatrics, Centre mère-enfant Soleil du CHU de Québec-Université Laval, Quebec, Quebec City, Canada.
Nat Genet ; 54(12): 1865-1880, 2022 12.
Article em En | MEDLINE | ID: mdl-36471070
ABSTRACT
Canonical (H3.1/H3.2) and noncanonical (H3.3) histone 3 K27M-mutant gliomas have unique spatiotemporal distributions, partner alterations and molecular profiles. The contribution of the cell of origin to these differences has been challenging to uncouple from the oncogenic reprogramming induced by the mutation. Here, we perform an integrated analysis of 116 tumors, including single-cell transcriptome and chromatin accessibility, 3D chromatin architecture and epigenomic profiles, and show that K27M-mutant gliomas faithfully maintain chromatin configuration at developmental genes consistent with anatomically distinct oligodendrocyte precursor cells (OPCs). H3.3K27M thalamic gliomas map to prosomere 2-derived lineages. In turn, H3.1K27M ACVR1-mutant pontine gliomas uniformly mirror early ventral NKX6-1+/SHH-dependent brainstem OPCs, whereas H3.3K27M gliomas frequently resemble dorsal PAX3+/BMP-dependent progenitors. Our data suggest a context-specific vulnerability in H3.1K27M-mutant SHH-dependent ventral OPCs, which rely on acquisition of ACVR1 mutations to drive aberrant BMP signaling required for oncogenesis. The unifying action of K27M mutations is to restrict H3K27me3 at PRC2 landing sites, whereas other epigenetic changes are mainly contingent on the cell of origin chromatin state and cycling rate.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Epigenômica Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Epigenômica Idioma: En Ano de publicação: 2022 Tipo de documento: Article