title: DNA methylation profiles distinguish different subtypes of gastroenteropancreatic neuroendocrine tumors.
abstract: OBJECTIVE
  Most studies have considered gastroenteropancreatic neuroendocrine tumors (GEP-NETs) as a homogenous group of samples or distinguish only gastrointestinal from pancreatic endocrine tumors. This article investigates if DNA methylation patterns could distinguish subtypes of GEP-NETs.
  
  
  METHODS
  The DNA methylation level of 807 cancer-related genes was investigated in insulinomas, gastrinomas, non-functioning pancreatic endocrine tumors and small intestine endocrine tumors.
  
  
  RESULTS
  DNA methylation patterns were found to be tumor type specific for each of the pancreatic tumor subtypes and identified two distinct methylation-based groups in small intestine endocrine tumors. Differences of DNA methylation levels were validated by pyrosequencing for 20 candidate genes and correlated with differences at the transcriptional level for four candidate genes.
  
  
  CONCLUSIONS
  The heterogeneity of DNA methylation patterns in the different subtypes of gastroenteropancreatic neuroendocrine tumors suggests different underlying pathways and, therefore, these tumors should be considered as distinct entities in molecular and clinical studies.
authors.affiliation: Laboratory for Epigenetics & Environment, Centre National de Génotypage, CEA-Institut de Génomique, Evry, France.|Laboratory for Functional Genomics, Fondation Jean Dausset - CEPH, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: How-Kit
authors.affiliation: Laboratory for Epigenetics & Environment, Centre National de Génotypage, CEA-Institut de Génomique, Evry, France.
authors.forename: Emelyne
authors.initials: E
authors.lastname: Dejeux
authors.affiliation: Service de chirurgie digestive, hépatobiliaire et endocrinienne, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dousset
authors.affiliation: Laboratory for Bioinformatics, Fondation Jean Dausset - CEPH, Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Renault
authors.affiliation: Laboratory for Epigenetics & Environment, Centre National de Génotypage, CEA-Institut de Génomique, Evry, France.|Laboratory for Functional Genomics, Fondation Jean Dausset - CEPH, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Baudry
authors.affiliation: Service d'Anatomie et de Cytologie Pathologique, Hôpital Cochin, AP-HP, Paris, France.|Institut Cochin de Génétique Moléculaire, Université Paris V René Descartes, CNRS (UMR8104), France.|Institut National de la Santé et de la Recherche Médicale U567, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Terris
authors.affiliation: Laboratory for Epigenetics & Environment, Centre National de Génotypage, CEA-Institut de Génomique, Evry, France.
authors.forename: Jörg
authors.initials: J
authors.lastname: Tost
mesh_terms: D002273:Carcinogens; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D016147:Genes, Tumor Suppressor; D056426:Genetic Loci; D006801:Humans; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D059467:Transcriptome
chemical_list: D002273:Carcinogens
keywords: DNA methylation; cancer; endocrine tumors; growth factors; insulinomas; pancreatic endocrine tumors; tumor classification