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Developmental basis of SHH medulloblastoma heterogeneity.
Gold, Maxwell P; Ong, Winnie; Masteller, Andrew M; Ghasemi, David R; Galindo, Julie Anne; Park, Noel R; Huynh, Nhan C; Donde, Aneesh; Pister, Veronika; Saurez, Raul A; Vladoiu, Maria C; Hwang, Grace H; Eisemann, Tanja; Donovan, Laura K; Walker, Adam D; Benetatos, Joseph; Dufour, Christelle; Garzia, Livia; Segal, Rosalind A; Wechsler-Reya, Robert J; Mesirov, Jill P; Korshunov, Andrey; Pajtler, Kristian W; Pomeroy, Scott L; Ayrault, Olivier; Davidson, Shawn M; Cotter, Jennifer A; Taylor, Michael D; Fraenkel, Ernest.
Afiliación
  • Gold MP; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Ong W; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Masteller AM; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Ghasemi DR; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Galindo JA; Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
  • Park NR; Division of Pediatric Neuro-oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Huynh NC; Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
  • Donde A; Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles (CHLA), Los Angeles, CA, USA.
  • Pister V; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
  • Saurez RA; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • Vladoiu MC; Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
  • Hwang GH; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Eisemann T; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Donovan LK; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Walker AD; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Benetatos J; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Dufour C; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Garzia L; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Segal RA; Cancer Genome and Epigenetics Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • Wechsler-Reya RJ; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Mesirov JP; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Korshunov A; Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles (CHLA), Los Angeles, CA, USA.
  • Pajtler KW; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Pomeroy SL; Department of Child and Adolescent Oncology, Gustave Roussy, Villejuif, France.
  • Ayrault O; INSERM U981, Molecular Predictors and New Targets in Oncology, University Paris-Saclay, Villejuif, France.
  • Davidson SM; Cancer Research Program, McGill University, Montreal, QC, Canada.
  • Cotter JA; MUHC Research Institute, McGill University, Montreal, QC, Canada.
  • Taylor MD; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Fraenkel E; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Nat Commun ; 15(1): 270, 2024 Jan 08.
Article en En | MEDLINE | ID: mdl-38191555
ABSTRACT
Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different developmental stages. Additionally, using multiplexed proteomic imaging and MALDI imaging mass spectrometry, we identify distinct histological and metabolic profiles for highly differentiated tumors. Our approaches are applicable to understanding the interplay between heterogeneity and differentiation in other cancers and can provide important insights for the design of targeted therapies.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Cerebelosas / Meduloblastoma Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Cerebelosas / Meduloblastoma Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos