Publication Date:
2011-01-22
Description:
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 (alpha 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144496/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144496/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiao, Yuchen -- Shi, Chanjuan -- Edil, Barish H -- de Wilde, Roeland F -- Klimstra, David S -- Maitra, Anirban -- Schulick, Richard D -- Tang, Laura H -- Wolfgang, Christopher L -- Choti, Michael A -- Velculescu, Victor E -- Diaz, Luis A Jr -- Vogelstein, Bert -- Kinzler, Kenneth W -- Hruban, Ralph H -- Papadopoulos, Nickolas -- CA121113/CA/NCI NIH HHS/ -- P01CA134292/CA/NCI NIH HHS/ -- P50 CA062924/CA/NCI NIH HHS/ -- P50 CA062924-12/CA/NCI NIH HHS/ -- P50CA062924/CA/NCI NIH HHS/ -- R01 CA113669/CA/NCI NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-05/CA/NCI NIH HHS/ -- R01CA113669/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Mar 4;331(6021):1199-203. doi: 10.1126/science.1200609. Epub 2011 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21252315" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/*genetics
;
Carcinoma, Pancreatic Ductal/genetics
;
Chromatin Assembly and Disassembly/genetics
;
DNA Helicases/*genetics
;
Genes, Tumor Suppressor
;
Humans
;
*Mutation
;
Neuroendocrine Tumors/*genetics/metabolism
;
Nuclear Proteins/*genetics
;
PTEN Phosphohydrolase/genetics
;
Pancreatic Neoplasms/*genetics/metabolism
;
Phosphatidylinositol 3-Kinases/genetics
;
Prognosis
;
Proto-Oncogene Proteins/*genetics
;
Sequence Analysis, DNA
;
Signal Transduction/genetics
;
TOR Serine-Threonine Kinases/genetics/*metabolism
;
Tumor Suppressor Proteins/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink