DNA methylation profiles distinguish different subtypes of gastroenteropancreatic neuroendocrine tumors

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 (NF-PETs) and small intestine endocrine tumors (SIETs). 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 SIETs. 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 GEP-NETs suggests different underlying pathways and, therefore, these tumors should be considered as distinct entities in molecular and clinical studies.