Genomic landscape in gastroenteropancreatic neuroendocrine neoplasms and its usefulness in improving the prognostic evaluation

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are a heterogenous group of tumors with Pancreatic and Small intestinal NET (PanNET and Si-NET) representing most of them. Despite the increased understanding based on advancements on genomic level, the possible implications for treatment remain elusive. PanNET and Si-NET are both characterized by a low mutation rate compared to other tumor entities. In addition, epigenetic changes seem to be important for tumor development, patient stratification and possibly for therapy. In PanNET four major pathways are affected by genetic and epigenetic alterations: chromatin modification and telomere maintenance, DNA damage, mTOR signalling and hypoxia. Notably, hypoxia signalling, mTOR pathway alteration and mutations in DAXX/ATRX are associated with aggressive behaviour. In si-NET alterations in DNA methylation and high copy number variation correlate with short survival.