Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy

Nat Rev Gastroenterol Hepatol. 2012 Feb 7;9(4):199-208. doi: 10.1038/nrgastro.2012.9.


Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise ∼1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of ∼65% and a 10-year survival of 45% for resected lesions. As PanNETs have a low incidence, they have been understudied, with few advances made until the completion of their exomic sequencing in the past year. In this Review, we summarize some of the latest insights into the genetics of PanNETs, and their probable implications in the context of prognosis and therapy. In particular, we discuss two genes (DAXX and ATRX) that have collectively been identified as mutated in >40% of PanNETs, and the biological and prognostic implications of these novel mutations. The identification of recurrent somatic mutations within the mTOR signaling pathway and the therapeutic implications for personalized therapy in patients with PanNETs are also discussed. Finally, this Review outlines state-of-the-art advances in the biology of PanNETs that are of emerging translational importance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Testing / methods
  • Humans
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / genetics*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics*
  • Pharmacogenetics / methods*
  • Precision Medicine / methods*