pancreatic neuroendocrine tumors 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 mutations in genes encoding either of the two subunits of a transcription / chromatin remodeling complex consisting of daxx and atrx . clinically , mutations in the men1 and daxx / atrx genes were associated with better prognosis . we also found mutations in genes in the mtor pathway in 14 % of the tumors , a finding that could potentially be used to stratify patients for treatment with mtor inhibitors .