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Hypermutation In Pancreatic Cancer.
Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew.
Afiliação
  • Humphris JL; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Patch AM; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Nones K; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Bailey PJ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
  • Johns AL; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • McKay S; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Chang DK; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wa
  • Miller DK; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Pajic M; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
  • Kassahn KS; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Genetic and Molecular Pathology, Adelaide, South Australia, Australia; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australi
  • Quinn MC; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Bruxner TJ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Christ AN; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Harliwong I; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Idrisoglu S; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Manning S; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Nourse C; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
  • Nourbakhsh E; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Stone A; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Wilson PJ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Anderson M; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Fink JL; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Holmes O; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Kazakoff S; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Leonard C; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Newell F; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Waddell N; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Wood S; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Mead RS; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; South Eastern Area Laboratory Services Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia; Sonic Genetics, Douglas
  • Xu Q; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Wu J; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Pinese M; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Cowley MJ; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
  • Jones MD; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
  • Nagrial AM; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Chin VT; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Chantrill LA; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales, Australia.
  • Mawson A; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Chou A; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Department of Anatomical Pathology, SydPath, St Vincent's Hospital, New South Wales, Australia.
  • Scarlett CJ; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia.
  • Pinho AV; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Rooman I; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Giry-Laterriere M; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Samra JS; Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia.
  • Kench JG; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperd
  • Merrett ND; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.
  • Toon CW; The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
  • Epari K; Department of Surgery, Fiona Stanley Hospital, Murdoch, Washington.
  • Nguyen NQ; Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia.
  • Barbour A; Department of Surgery, Princess Alexandra Hospital, Woollongabba, Queensland, Australia.
Gastroenterology ; 152(1): 68-74.e2, 2017 01.
Article em En | MEDLINE | ID: mdl-27856273
ABSTRACT
Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Reparo de Erro de Pareamento de DNA / Transcriptoma / Mutação Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Gastroenterology Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Reparo de Erro de Pareamento de DNA / Transcriptoma / Mutação Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Gastroenterology Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Austrália