Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy

被引：85

作者：

de Wilde, Roeland F. ^{[1
]}

Edil, Barish H. ^{[2
]}

Hruban, Ralph H. ^{[1
]}

Maitra, Anirban ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA

[2] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21231 USA

来源：

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY | 2012年 / 9卷 / 04期

关键词：

MULTIPLE ENDOCRINE NEOPLASIA; ISLET-CELL-CARCINOMA; HIPPEL-LINDAU-DISEASE; TELOMERE MAINTENANCE MECHANISM; MOUSE MODEL; CHROMOSOMAL INSTABILITY; ANTITUMOR-ACTIVITY; SURVIVAL BENEFIT; MTOR PATHWAY; PHASE-II;

D O I：

10.1038/nrgastro.2012.9

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：199 / 208

页数：10