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These differences may have roots in genomic and epigenetic differences, but the rarity of GEP-NETs has limited the progress of large-scale comprehensive analyses that could provide definitive insight into oncogenic molecular mechanisms. The incidence of GEP-NETs has risen from 1.00 in 1977 to 3.00 in 2007, with site-specific tumor incidence and behavior varying widely. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of rare tumors thought to arise from the malignant transformation of neuroendocrine cells located in the digestive tract. Overview of gastroenteropancreatic neuroendocrine tumors Furthermore, these findings form the foundation for future studies evaluating the clinical efficacy of epigenetic modifications as prognostic biomarkers, as well as potential therapeutic targets. Nevertheless, there are many opportunities to further define the mechanisms by which these epigenetic modifications influence tumorigenesis, and this will provide better insight into their prognostic and therapeutic utility. Several translational studies have provided convincing data identifying potential prognostic biomarkers, and some of these have demonstrated preliminary success as serum biomarkers that can be used clinically. Despite the heterogeneity of tumor cohorts evaluated in these studies, it is obvious that there are methylation patterns, chromatin remodeling alterations, and microRNA and long non-coding RNA (lncRNA) differential expression profiles that are distinctive of GEP-NETs, some of which are correlated with significant differences in clinical outcomes. Accordingly, the dysregulation of epigenetic mechanisms has been hypothesized as a potential regulator of GEP-NET tumorigenesis and has become a major focus of recent studies.

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Even within GEP-NETs, there are no common oncogenic drivers for example, DAXX/ ATRX mutations are strongly implicated in the tumorigenesis of pancreatic but not small bowel NETs. Genetic alterations associated with familial inherited syndromes have been well defined however, the genetic profile of sporadic tumors is less clear as their tumorigenesis does not appear to be controlled by classic oncogenes such as P53, RB, or KRAS. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of rare tumors whose site-specific tumor incidence and clinical behavior vary widely.

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