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. 2011 Mar 4;331(6021):1199-203.
doi: 10.1126/science.1200609. Epub 2011 Jan 20.

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

Yuchen Jiao  1 , Chanjuan Shi, Barish H Edil, Roeland F de Wilde, David S Klimstra, Anirban Maitra, Richard D Schulick, Laura H Tang, Christopher L Wolfgang, Michael A Choti, Victor E Velculescu, Luis A Diaz Jr, Bert Vogelstein, Kenneth W Kinzler, Ralph H Hruban, Nickolas Papadopoulos
Affiliations

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

Yuchen Jiao et al. Science. .

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.

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Comment in

  • Cancer. New epigenetic drivers of cancers.
    Elsässer SJ, Allis CD, Lewis PW. Elsässer SJ, et al. Science. 2011 Mar 4;331(6021):1145-6. doi: 10.1126/science.1203280. Science. 2011. PMID: 21385704 No abstract available.

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