Divergent clonal selection dominates medulloblastoma at recurrence.

Autor: Morrissy AS; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Garzia L; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Shih DJ; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada., Zuyderduyn S; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada., Huang X; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada., Skowron P; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada., Remke M; Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Düsseldorf, M5S 3E1, Germany., Cavalli FM; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Ramaswamy V; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada.; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada., Lindsay PE; Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9, Canada.; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada., Jelveh S; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada., Donovan LK; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Wang X; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada., Luu B; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Zayne K; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Li Y; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Mayoh C; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Thiessen N; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Mercier E; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Mungall KL; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Ma Y; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Tse K; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Zeng T; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Shumansky K; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada., Roth AJ; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada., Shah S; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada., Farooq H; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Kijima N; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Holgado BL; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Lee JJ; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada., Matan-Lithwick S; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Liu J; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Mack SC; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Center for Stem Cell &Regenerative Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA., Manno A; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Michealraj KA; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Nor C; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Peacock J; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada., Qin L; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Reimand J; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada., Rolider A; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Thompson YY; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada., Wu X; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada., Pugh T; Clinical Genomics Research Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario 44195, Canada., Ally A; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Bilenky M; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Butterfield YS; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Carlsen R; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Cheng Y; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Chuah E; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Corbett RD; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Dhalla N; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., He A; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Lee D; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Li HI; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Long W; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Mayo M; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Plettner P; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Qian JQ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Schein JE; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Tam A; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Wong T; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Birol I; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.; School of Computing Science, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada., Zhao Y; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Faria CC; Division of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal., Pimentel J; Divison of Pathology, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon 1649-035, Portugal., Nunes S; Unidade de Neuro-Oncologia Pediátrica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon 1099-023, Portugal., Shalaby T; Departments of Oncology and Neuro-Oncology, University Children's Hospital of Zurich, Zurich 8032, Switzerland., Grotzer M; Departments of Oncology and Neuro-Oncology, University Children's Hospital of Zurich, Zurich 8032, Switzerland., Pollack IF; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA., Hamilton RL; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA., Li XN; Brain Tumor Program, Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA., Bendel AE; Pediatric Hematology-Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota 55404, USA., Fults DW; Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah 84132, USA., Walter AW; A I duPont Hospital for Children, Wilmington, Delaware 19803, USA., Kumabe T; Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan., Tominaga T; Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan., Collins VP; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK., Cho YJ; Departments of Neurosurgery, Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA., Hoffman C; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada., Lyden D; Departments of Pediatrics, Cell &Developmental Biology, Weill Medical College of Cornell University, New York, New York 10065, USA., Wisoff JH; Department of Neurosurgery, NYU Langone Medical Center, New York, New York 10016, USA., Garvin JH Jr; Department of Pediatrics, Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University, New York, New York 10032, USA., Stearns DS; Department of Pediatrics-Hematology and Oncology, Rainbow Babies &Children's Hospital and Department of Pediatrics-Hematology and Oncology, Case Western Reserve, Cleveland, Ohio 44106, USA., Massimi L; Pediatric Neurosurgery, Catholic University Medical School, Rome 00198, Italy., Schüller U; Center for Neuropathology, Ludwig-Maximilians-Universität, Munich 81377, Germany., Sterba J; Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno 625 00, Czech Republic., Zitterbart K; Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno 625 00, Czech Republic., Puget S; AP-HP, Department of Neurosurgery, Necker-Enfants Malades Hospital, Université René Descartes, Paris 75743, France., Ayrault O; Signaling in Development and Brain Tumors, CNRS UMR 3347 / INSERM U1021, Institut Curie, Paris Cedex 5 91405, France., Dunn SE; Division of Hematology/Oncology, British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada., Tirapelli DP; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil, Rebeirao Preto, São Paulo 14049-900, Brazil., Carlotti CG; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil, Rebeirao Preto, São Paulo 14049-900, Brazil., Wheeler H; Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales 2065, Australia., Hallahan AR; Queensland Children's Medical Research Institute, Children's Health Queensland, Brisbane, Queensland 4029, Australia.; Division of Oncology, Children's Health Queensland, Brisbane, Queensland 4029, Australia., Ingram W; Queensland Children's Medical Research Institute, Children's Health Queensland, Brisbane, Queensland 4029, Australia.; UQ Child Health Research Centre, The University of Queensland, Brisbane 4029, Australia., MacDonald TJ; Pediatric Neuro-Oncology Program, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30307, USA., Olson JJ; Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA., Van Meir EG; Department of Hematology &Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA., Lee JY; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea., Wang KC; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea., Kim SK; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea., Cho BK; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea., Pietsch T; Institute for Neuropathology, University of Bonn D-53105, Germany., Fleischhack G; Children's University Hospital of Essen D-45147, Germany., Tippelt S; Children's University Hospital of Essen D-45147, Germany., Ra YS; Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul 05505, South Korea., Bailey S; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, UK., Lindsey JC; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, UK., Clifford SC; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, UK., Eberhart CG; Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA., Cooper MK; Department of Neurology, Vanderbilt Medical Center, Nashville, Tennessee 37232-8550, USA., Packer RJ; Department of Neurology, Children's National Medical Center, Washington DC 20010-2970, USA., Massimino M; Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, Italy., Garre ML; U.O. Neurochirurgia, Istituto Giannina Gaslini, Genova 16147, Italy., Bartels U; Department of Haematology &Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada., Tabori U; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Haematology &Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada., Hawkins CE; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Division of Pathology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada., Dirks P; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada., Bouffet E; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Haematology &Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada., Rutka JT; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada.; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada., Wechsler-Reya RJ; Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA., Weiss WA; Departments of Pediatrics, Neurology and Neurosurgery, University of California San Francisco, San Francisco, California 94158, USA., Collier LS; School of Pharmacology, University of Wisconsin, Madison, Wisconsin 53715, USA., Dupuy AJ; Molecular &Cellular Biology Program, University of Iowa, Iowa City, Iowa 52242, USA., Korshunov A; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany., Jones DT; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany., Kool M; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany., Northcott PA; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany., Pfister SM; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.; Department of Pediatric Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany., Largaespada DA; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA., Mungall AJ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Moore RA; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada., Jabado N; Division of Hematology/Oncology, McGill University, Montreal, Quebec H2W 1S6., Canada., Bader GD; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.; McLaughlin Centre and Department of Molecular Genetics, Banting and Best Department of Medical Research and Samuel Lunenfeld Research Institute at Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1L7, Canada., Jones SJ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.; Department of Molecular Biology &Biochemistry, Simon Fraser University, Burnaby, British Columbia M5G 1L7, Canada., Malkin D; Department of Haematology &Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.; Department of Pediatrics, University of Toronto, Toronto, Ontario M5G 1X8, Canada., Marra MA; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada., Taylor MD; Developmental &Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 0A4, Canada.; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario M5S 3E1, Canada.
Jazyk: angličtina
Zdroj: Nature [Nature] 2016 Jan 21; Vol. 529 (7586), pp. 351-7. Date of Electronic Publication: 2016 Jan 13.
DOI: 10.1038/nature16478
Abstrakt: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
Databáze: MEDLINE