Molecular Genetics of Gastroenteropancreatic Neuroendocrine Tumours

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) can be divided to subgroups depending on their localization. Genetics of pancreatic neuroendocrine tumours (PNETs) is relatively well characterized, with frequent germline or somatic mutations in MEN1, VHL, TSC1/TSC2 and NF1 and somatic mutations in ATRX/DAXX, YY1 as well as members of the mTOR signalling pathway. Mutations in YY1 have so far been reported only in insulin-producing tumours. Most frequent chromosomal aberrations were observed in 6q, 11q, 11p, 20p and 21. The genetics of small intestinal neuroendocrine tumours is, however, more or less unknown. On the other hand, more information about chromosomal aberrations has been reported, pointing out chromosome 18 and 11 as being frequently altered in SI-NETs. While a significant portion of PNETs is part of familial syndromes with known genetic background, almost no information is available for other gastroenteropancreatic neuroendocrine tumours. In this chapter we present the current knowledge of genetics involved in gastroenteropancreatic neuroendocrine tumorigenesis.