Alexandre How-Kit1,2, Emelyne Dejeux1, Bertrand Dousset3, Victor Renault4, Marion Baudry1,2, Benoit Terris5,6,7, Jörg Tost1. 1. Laboratory for Epigenetics & Environment, Centre National de Génotypage, CEA-Institut de Génomique, Evry, France. 2. Laboratory for Functional Genomics, Fondation Jean Dausset - CEPH, Paris, France. 3. Service de chirurgie digestive, hépatobiliaire et endocrinienne, Hôpital Cochin, AP-HP, Paris, France. 4. Laboratory for Bioinformatics, Fondation Jean Dausset - CEPH, Paris, France. 5. Service d'Anatomie et de Cytologie Pathologique, Hôpital Cochin, AP-HP, Paris, France. 6. Institut Cochin de Génétique Moléculaire, Université Paris V René Descartes, CNRS (UMR8104), France. 7. Institut National de la Santé et de la Recherche Médicale U567, Paris, France.
Abstract
AIM: 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. MATERIALS & 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. CONCLUSION: 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.
AIM: 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. MATERIALS & 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. CONCLUSION: 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.