DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors Journal Article
| Authors: | Jiao, Y.; Shi, C.; Edil, B. H.; de Wilde, R. F.; Klimstra, D. S.; Maitra, A.; Schulick, R. D.; Tang, L. H.; Wolfgang, C. L.; Choti, M. A.; Velculescu, V. E.; Diaz, L. A. Jr; Vogelstein, B.; Kinzler, K. W.; Hruban, R. H.; Papadopoulos, N. |
| Article Title: | DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors |
| 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. |
| Keywords: | signal transduction; human tissue; unclassified drug; oncoprotein; gene mutation; mutation; proto-oncogene proteins; pancreatic neoplasms; genetic analysis; mammalia; carcinoma, pancreatic ductal; genetic association; enzyme activity; nuclear proteins; neuroendocrine tumor; pancreas tumor; mammalian target of rapamycin; tumor suppressor proteins; pten phosphohydrolase; adaptor proteins, signal transducing; tumor; methionine; dna helicases; genes, tumor suppressor; chromatin assembly and disassembly; neuroendocrine tumors; sequence analysis, dna; phosphatidylinositol 3-kinases; death domain associated protein; protein alpha thalassemia mental retardation syndrome x linked; pancreatic neuroendocrine tumor; tor serine-threonine kinases |
| Journal Title: | Science |
| Volume: | 331 |
| Issue: | 6021 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2011-03-04 |
| Start Page: | 1199 |
| End Page: | 1203 |
| Language: | English |
| DOI: | 10.1126/science.1200609 |
| PUBMED: | 21252315 |
| PROVIDER: | scopus |
| PMCID: | PMC3144496 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 23 June 2011" - "CODEN: SCIEA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work