DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.

Journal Article (Journal Article)

Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1, which encodes menin, a component of a histone methyltransferase complex, and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX (α thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.

Full Text

Duke Authors

Cited Authors

  • Jiao, Y; Shi, C; Edil, BH; de Wilde, RF; Klimstra, DS; Maitra, A; Schulick, RD; Tang, LH; Wolfgang, CL; Choti, MA; Velculescu, VE; Diaz, LA; Vogelstein, B; Kinzler, KW; Hruban, RH; Papadopoulos, N

Published Date

  • March 4, 2011

Published In

Volume / Issue

  • 331 / 6021

Start / End Page

  • 1199 - 1203

PubMed ID

  • 21252315

Pubmed Central ID

  • PMC3144496

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1200609


  • eng

Conference Location

  • United States