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Author Manuscript
Science. Author manuscript; available in PMC 2011 July 27.
Published in final edited form as: Science. 2011 March 4; 331(6021): 1199–1203. doi:10.1126/science.1200609.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDAXX/ATRX, MEN1 and mTOR Pathway Genes are Frequently Altered in Pancreatic Neuroendocrine Tumors
Yuchen Jiao1,*, Chanjuan Shi2,*, Barish H. Edil3, Roeland F. de Wilde2, David S. Klimstra4, Anirban Maitra5, Richard D. Schulick3, Laura H. Tang4, Christopher L. Wolfgang3, Michael A. Choti3, Victor E. Velculescu1, Luis A. Diaz Jr.1,6, Bert Vogelstein1, Kenneth W. Kinzler1,+, Ralph H. Hruban5,+, and Nickolas Papadopoulos1,+ 1Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231
2Departmentof Pathology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions, Baltimore, MD 21231
3Departmentof Surgery, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions, Baltimore, MD 21231
4Departmentof Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 100655Departmentsof Pathology and Oncology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions, Baltimore, MD 21231
6SwimAcross America Laboratory at Johns Hopkins, Baltimore, MD 21231Abstract
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 ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had…

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