DAXX / ATRX , MEN1 , and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors

作者：Yuchen Jiao, Chanjuan Shi, Barish H. Edil, Roeland F. de Wilde, David S. Klimstra, Anirban Maitra, Richard David Schulick, Laura H. Tang, Christopher Lee Wolfgang, Michael A. Choti, Victor E. Velculescu, Luis Alberto Diaz, Bert Vogelstein, Kenneth W. Kinzler, Ralph H. Hruban, Nickolas Papadopoulos · 发表于：Science · 年份：2011 · DOI：10.1126/science.1200609 · 被引用次数：1730 · 研究领域：Neuroendocrine Tumor Research Advances、Neuroblastoma Research and Treatments、PI3K/AKT/mTOR signaling in cancer

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.