TY - JOUR
T1 - Well-differentiated pancreatic neuroendocrine tumors
T2 - From genetics to therapy
AU - De Wilde, Roeland F.
AU - Edil, Barish H.
AU - Hruban, Ralph H.
AU - Maitra, Anirban
N1 - Funding Information:
The authors would like to acknowledge the support of the Sol Goldman Pancreatic Cancer Research Center and the Caring for Carcinoid Foundation. The authors are grateful to Drs Alan Meeker and Christopher Heaphy (Johns Hopkins University) for assistance with Figure 3 of this Review and helpful suggestions.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
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U2 - 10.1038/nrgastro.2012.9
DO - 10.1038/nrgastro.2012.9
M3 - Review article
C2 - 22310917
AN - SCOPUS:84859442623
VL - 9
SP - 199
EP - 208
JO - Nature Reviews Gastroenterology and Hepatology
JF - Nature Reviews Gastroenterology and Hepatology
SN - 1759-5045
IS - 4
ER -