Exomic sequencing of pancreatic neuroendocrine tumors: Detection of alterations in chromatin remodeling and mTOR pathway genes.

摘要: 10501 Background: Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia relatively little is known about the molecular genetics this disease. Methods: To explore genetic basis PanNETs, we determined exomic sequences ten non-familial PanNETs and then screened most commonly mutated genes in 58 additional PanNETs. Results: We found frequently implicated chromatin remodeling: 44% tumors had somatic inactivating mutations MEN-1, which encodes menin, component histone methyltransferase complex; 43% encoding either two subunits transcription/chromatin remodeling complex consisting DAXX (death-domain associated protein) ATRX (alpha thalassemia/mental retardation syndrome X-linked). In multivariate analysis adjusting for WHO classification, MEN1 (HR 0.30; 95% CI 0.1-0.9; p=0.03) DAXX/ATRX 0.23; 0.07-0.75; p=0.02) genes, alon...