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Spatial heterogeneity in medulloblastoma.
Morrissy, A Sorana; Cavalli, Florence M G; Remke, Marc; Ramaswamy, Vijay; Shih, David J H; Holgado, Borja L; Farooq, Hamza; Donovan, Laura K; Garzia, Livia; Agnihotri, Sameer; Kiehna, Erin N; Mercier, Eloi; Mayoh, Chelsea; Papillon-Cavanagh, Simon; Nikbakht, Hamid; Gayden, Tenzin; Torchia, Jonathon; Picard, Daniel; Merino, Diana M; Vladoiu, Maria; Luu, Betty; Wu, Xiaochong; Daniels, Craig; Horswell, Stuart; Thompson, Yuan Yao; Hovestadt, Volker; Northcott, Paul A; Jones, David T W; Peacock, John; Wang, Xin; Mack, Stephen C; Reimand, Jüri; Albrecht, Steffen; Fontebasso, Adam M; Thiessen, Nina; Li, Yisu; Schein, Jacqueline E; Lee, Darlene; Carlsen, Rebecca; Mayo, Michael; Tse, Kane; Tam, Angela; Dhalla, Noreen; Ally, Adrian; Chuah, Eric; Cheng, Young; Plettner, Patrick; Li, Haiyan I; Corbett, Richard D; Wong, Tina.
Affiliation
  • Morrissy AS; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Cavalli FMG; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Remke M; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Ramaswamy V; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Shih DJH; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Holgado BL; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Farooq H; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Donovan LK; Department of Neuropathology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Garzia L; Department of Pediatric Neuro-Oncogenomics, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Düsseldorf, Germany.
  • Agnihotri S; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Kiehna EN; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Mercier E; Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Mayoh C; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Papillon-Cavanagh S; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Nikbakht H; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Gayden T; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Torchia J; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Picard D; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Merino DM; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Vladoiu M; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Luu B; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Wu X; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Daniels C; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Horswell S; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Thompson YY; Cancer Research Program, McGill University Health Centre Research Institute, Montreal, Quebec, Canada.
  • Hovestadt V; MacFeeters-Hamilton Brain Tumour Centre, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Northcott PA; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Jones DTW; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Peacock J; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Wang X; Departments of Pediatrics and Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Mack SC; Departments of Pediatrics and Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Reimand J; Departments of Pediatrics and Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Albrecht S; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Fontebasso AM; Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Thiessen N; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Li Y; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Schein JE; Department of Neuropathology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Lee D; Department of Pediatric Neuro-Oncogenomics, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Düsseldorf, Germany.
  • Carlsen R; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Mayo M; Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Tse K; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Tam A; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Dhalla N; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Ally A; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Chuah E; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Cheng Y; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Plettner P; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Li HI; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Corbett RD; Cancer Research UK London Research Institute, London, UK.
  • Wong T; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Nat Genet ; 49(5): 780-788, 2017 May.
Article in En | MEDLINE | ID: mdl-28394352
ABSTRACT
Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Cerebellar Neoplasms / Transcriptome / Medulloblastoma Limits: Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Male / Middle aged Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2017 Document type: Article Affiliation country: Canadá
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Cerebellar Neoplasms / Transcriptome / Medulloblastoma Limits: Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Male / Middle aged Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2017 Document type: Article Affiliation country: Canadá