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The transcriptional landscape of Shh medulloblastoma.
Skowron, Patryk; Farooq, Hamza; Cavalli, Florence M G; Morrissy, A Sorana; Ly, Michelle; Hendrikse, Liam D; Wang, Evan Y; Djambazian, Haig; Zhu, Helen; Mungall, Karen L; Trinh, Quang M; Zheng, Tina; Dai, Shizhong; Stucklin, Ana S Guerreiro; Vladoiu, Maria C; Fong, Vernon; Holgado, Borja L; Nor, Carolina; Wu, Xiaochong; Abd-Rabbo, Diala; Bérubé, Pierre; Wang, Yu Chang; Luu, Betty; Suarez, Raul A; Rastan, Avesta; Gillmor, Aaron H; Lee, John J Y; Zhang, Xiao Yun; Daniels, Craig; Dirks, Peter; Malkin, David; Bouffet, Eric; Tabori, Uri; Loukides, James; Doz, François P; Bourdeaut, Franck; Delattre, Olivier O; Masliah-Planchon, Julien; Ayrault, Olivier; Kim, Seung-Ki; Meyronet, David; Grajkowska, Wieslawa A; Carlotti, Carlos G; de Torres, Carmen; Mora, Jaume; Eberhart, Charles G; Van Meir, Erwin G; Kumabe, Toshihiro; French, Pim J; Kros, Johan M.
Affiliation
  • Skowron P; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Farooq H; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Cavalli FMG; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Morrissy AS; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Ly M; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Hendrikse LD; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Wang EY; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Djambazian H; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Zhu H; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Mungall KL; Alberta Children's Hospital Research Institute, Calgary, AB, Canada.
  • Trinh QM; Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.
  • Zheng T; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Dai S; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Stucklin ASG; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Vladoiu MC; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Fong V; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Holgado BL; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Nor C; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Wu X; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Abd-Rabbo D; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Bérubé P; McGill University Genome Centre, McGill University, Montreal, QC, Canada.
  • Wang YC; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Luu B; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Suarez RA; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • Rastan A; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Gillmor AH; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • Lee JJY; Department of Neurology, University of California San Francisco, San Francisco, CA, United States.
  • Zhang XY; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, United States.
  • Daniels C; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Dirks P; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Malkin D; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Bouffet E; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Tabori U; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Loukides J; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Doz FP; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Bourdeaut F; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Delattre OO; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Masliah-Planchon J; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Ayrault O; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Kim SK; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Meyronet D; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Grajkowska WA; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • Carlotti CG; McGill University Genome Centre, McGill University, Montreal, QC, Canada.
  • de Torres C; McGill University Genome Centre, McGill University, Montreal, QC, Canada.
  • Mora J; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Eberhart CG; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • Van Meir EG; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Kumabe T; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
  • French PJ; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Kros JM; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Nat Commun ; 12(1): 1749, 2021 03 19.
Article in En | MEDLINE | ID: mdl-33741928
ABSTRACT
Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Cerebellar Neoplasms / Hedgehog Proteins / Transcriptome / Medulloblastoma Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country: Canada
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Cerebellar Neoplasms / Hedgehog Proteins / Transcriptome / Medulloblastoma Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country: Canada