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Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis.
Nones, Katia; Waddell, Nicola; Wayte, Nicci; Patch, Ann-Marie; Bailey, Peter; Newell, Felicity; Holmes, Oliver; Fink, J Lynn; Quinn, Michael C J; Tang, Yue Hang; Lampe, Guy; Quek, Kelly; Loffler, Kelly A; Manning, Suzanne; Idrisoglu, Senel; Miller, David; Xu, Qinying; Waddell, Nick; Wilson, Peter J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Nourse, Craig; Nourbakhsh, Ehsan; Anderson, Matthew; Kazakoff, Stephen; Leonard, Conrad; Wood, Scott; Simpson, Peter T; Reid, Lynne E; Krause, Lutz; Hussey, Damian J; Watson, David I; Lord, Reginald V; Nancarrow, Derek; Phillips, Wayne A; Gotley, David; Smithers, B Mark; Whiteman, David C; Hayward, Nicholas K; Campbell, Peter J; Pearson, John V; Grimmond, Sean M; Barbour, Andrew P.
Afiliação
  • Nones K; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Waddell N; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Wayte N; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Patch AM; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Bailey P; Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Newell F; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Holmes O; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Fink JL; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Quinn MCJ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Tang YH; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Lampe G; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Quek K; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Loffler KA; Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Manning S; Department of Anatomical Pathology, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Idrisoglu S; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Miller D; Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Xu Q; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Waddell N; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Wilson PJ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Bruxner TJC; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Christ AN; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Harliwong I; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Nourse C; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Nourbakhsh E; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Anderson M; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Kazakoff S; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Leonard C; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Wood S; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Simpson PT; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Reid LE; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Krause L; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Hussey DJ; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Watson DI; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
  • Lord RV; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Nancarrow D; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Phillips WA; The University of Queensland, UQ Centre for Clinical Research, Herston, Brisbane, Queensland 4029, Australia.
  • Gotley D; The University of Queensland, School of Medicine, Herston, Queensland 4006, Australia.
  • Smithers BM; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Whiteman DC; The University of Queensland, UQ Centre for Clinical Research, Herston, Brisbane, Queensland 4029, Australia.
  • Hayward NK; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
  • Campbell PJ; Flinders University Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia.
  • Pearson JV; Flinders University Department of Surgery, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia.
  • Grimmond SM; St Vincent's Centre for Applied Medical Research, University of Notre Dame and University of New South Wales, Sydney, New South Wales 2011, Australia.
  • Barbour AP; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia.
Nat Commun ; 5: 5224, 2014 Oct 29.
Article em En | MEDLINE | ID: mdl-25351503
ABSTRACT
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Rearranjo Gênico / Adenocarcinoma / Genoma Humano / Carcinogênese Tipo de estudo: Screening_studies Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Rearranjo Gênico / Adenocarcinoma / Genoma Humano / Carcinogênese Tipo de estudo: Screening_studies Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article