Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy

作者：de Wilde Roeland F; Edil Barish H; Hruban Ralph H; Maitra Anirban^*

来源：Nature Reviews Gastroenterology & Hepatology, 2012, 9(4): 199-208.

DOI：10.1038/nrgastro.2012.9

Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise similar to 1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of similar to 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.

• 出版日期2012-4