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Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.
Krause, Lutz; Nones, Katia; Loffler, Kelly A; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J; Watson, David I; Lord, Reginald V; Phillips, Wayne A; Gotley, David; Smithers, B Mark; Whiteman, David C; Hayward, Nicholas K; Grimmond, Sean M; Waddell, Nicola; Barbour, Andrew P.
  • Krause L; Diamantina Institute, Translational Research Institute, The University of Queensland, Woolloongabba, Brisbane, Queensland 4102, Australia, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia.
  • Nones K; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia, Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia 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.
  • Nancarrow D; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia.
  • Oey H; Diamantina Institute, Translational Research Institute, The University of Queensland, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Tang YH; Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Wayte NJ; Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Patch AM; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia, Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
  • Patel K; Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia, Mater Medical Research Institute, Level 3 Aubigny Place, Raymond Terrace, Brisbane, Queensland 4101, Au
  • Brosda S; Diamantina Institute, Translational Research Institute, The University of Queensland, Woolloongabba, Brisbane, Queensland 4102, Australia, Faculty of Technology and Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany.
  • Manning S; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
  • Lampe G; Department of Anatomical Pathology, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Clouston A; School of Medicine, Centre for Liver Disease Research, The University of Queensland, 1/49 Butterfield Street, Herston, Brisbane, Queensland 4006, Australia.
  • Thomas J; Upper GI Research Unit, Division of Surgery, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia.
  • Stoye J; Faculty of Technology and Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany.
  • Hussey DJ; Department of Surgery, Flinders Medical Centre, Flinders University, Bedford Park, South Australia 5042, Australia.
  • Watson DI; Department of Surgery, Flinders Medical Centre, Flinders University, Bedford Park, South Australia 5042, Australia.
  • Lord RV; St. Vincent's Centre for Applied Medical Research, Sydney, New South Wales 2011, Australia, University of Notre Dame, Sydney, New South Wales 2011, Australia, University of New South Wales, Sydney, New South Wales 2011, Australia.
  • Phillips WA; Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia, Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia.
  • Gotley D; Department of Surgery, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia and.
  • Smithers BM; Department of Surgery, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia and.
  • Whiteman DC; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia.
  • Hayward NK; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia.
  • Grimmond SM; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia, Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow Scotland G61 1BD, UK.
  • Waddell N; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia, Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia, nic.waddell@qimrberghofer.edu.au.
  • Barbour AP; Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland 4102, Australia, Department of Surgery, School of Medicine, The University of Queensland, Princess Alexandra Hospital, W
Carcinogenesis ; 37(4): 356-65, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26905591
ABSTRACT
The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Adenocarcinoma / Metilación de ADN / Segregación Cromosómica / Huso Acromático Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Año: 2016 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Adenocarcinoma / Metilación de ADN / Segregación Cromosómica / Huso Acromático Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Año: 2016 Tipo del documento: Article