DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors Academic Article uri icon

Overview

MeSH Major

  • Adaptor Proteins, Signal Transducing
  • DNA Helicases
  • Mutation
  • Neuroendocrine Tumors
  • Nuclear Proteins
  • Pancreatic Neoplasms
  • Proto-Oncogene Proteins
  • TOR Serine-Threonine Kinases

abstract

  • 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.

publication date

  • March 4, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3144496

Digital Object Identifier (DOI)

  • 10.1126/science.1200609

PubMed ID

  • 21252315

Additional Document Info

start page

  • 1199

end page

  • 203

volume

  • 331

number

  • 6021