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Comprehensive Analysis of Hypermutation in Human Cancer.
Campbell, Brittany B; Light, Nicholas; Fabrizio, David; Zatzman, Matthew; Fuligni, Fabio; de Borja, Richard; Davidson, Scott; Edwards, Melissa; Elvin, Julia A; Hodel, Karl P; Zahurancik, Walter J; Suo, Zucai; Lipman, Tatiana; Wimmer, Katharina; Kratz, Christian P; Bowers, Daniel C; Laetsch, Theodore W; Dunn, Gavin P; Johanns, Tanner M; Grimmer, Matthew R; Smirnov, Ivan V; Larouche, Valérie; Samuel, David; Bronsema, Annika; Osborn, Michael; Stearns, Duncan; Raman, Pichai; Cole, Kristina A; Storm, Phillip B; Yalon, Michal; Opocher, Enrico; Mason, Gary; Thomas, Gregory A; Sabel, Magnus; George, Ben; Ziegler, David S; Lindhorst, Scott; Issai, Vanan Magimairajan; Constantini, Shlomi; Toledano, Helen; Elhasid, Ronit; Farah, Roula; Dvir, Rina; Dirks, Peter; Huang, Annie; Galati, Melissa A; Chung, Jiil; Ramaswamy, Vijay; Irwin, Meredith S; Aronson, Melyssa.
  • Campbell BB; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Light N; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Fabrizio D; Foundation Medicine, Inc., Cambridge, MA, USA.
  • Zatzman M; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Fuligni F; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
  • de Borja R; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
  • Davidson S; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
  • Edwards M; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
  • Elvin JA; Foundation Medicine, Inc., Cambridge, MA, USA.
  • Hodel KP; Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.
  • Zahurancik WJ; The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH, USA; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
  • Suo Z; The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH, USA; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
  • Lipman T; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
  • Wimmer K; Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
  • Kratz CP; Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
  • Bowers DC; Department of Pediatrics and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Health, Dallas, TX, USA.
  • Laetsch TW; Department of Pediatrics and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Health, Dallas, TX, USA.
  • Dunn GP; Department of Neurological Surgery, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
  • Johanns TM; Department of Neurological Surgery, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Grimmer MR; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Smirnov IV; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Larouche V; Department of Pediatrics, Centre Mère-enfant Soleil du CHU de Québec, CRCHU de Québec, Université Laval, Quebec City, QC, Canada.
  • Samuel D; Department of Hematology-Oncology, Valley Children's Hospital, Madera, CA, USA.
  • Bronsema A; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Osborn M; Department of Haematology and Oncology, Women's and Children's Hospital, North Adelaide, SA, Australia.
  • Stearns D; Department of Pediatrics-Hematology and Oncology, UH Rainbow Babies and Children's Hospital, Cleveland, OH, USA.
  • Raman P; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Cole KA; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Storm PB; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Yalon M; Department of Pediatric Hematology-Oncology, Sheba Medical Center, Tel Hashomer, Israel.
  • Opocher E; Pediatric Oncology & Hematology, Azienda Ospedaliera-Università degli Studi di Padova, Via Giustiniani n.1, Padova, Italy.
  • Mason G; Department of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
  • Thomas GA; Division of Pediatric Hematology-Oncology, Oregon Health & Science University, Portland, OR, USA.
  • Sabel M; Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg & Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • George B; Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Ziegler DS; Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia; Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Randwick, NSW, Australia.
  • Lindhorst S; Neuro-Oncology, Department of Neurosurgery, and Department of Medicine, Division of Hematology/Medical Oncology, Medical University of South Carolina, Charleston, SC, USA.
  • Issai VM; Department of Pediatric Hematology-Oncology, Cancer Care Manitoba; Research Institute in Oncology and Hematology (RIOH), University of Manitoba, Winnipeg, MB, Canada.
  • Constantini S; Department of Pediatric Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
  • Toledano H; Department of Pediatric Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
  • Elhasid R; Department of Hematology-Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • Farah R; Department of Pediatrics, Saint George Hospital University Medical Center, Beirut, Lebanon.
  • Dvir R; Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Dirks P; Department of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.
  • Huang A; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Galati MA; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
  • Chung J; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
  • Ramaswamy V; Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
  • Irwin MS; Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
  • Aronson M; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada.
Cell ; 171(5): 1042-1056.e10, 2017 Nov 16.
Article en En | MEDLINE | ID: mdl-29056344
ABSTRACT
We present an extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Tipo de estudio: Prognostic_studies Límite: Adult / Child / Humans Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
Imprimir
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PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Tipo de estudio: Prognostic_studies Límite: Adult / Child / Humans Idioma: En Año: 2017 Tipo del documento: Article