title: Mutational analysis of p27 (CDKN1B) and p18 (CDKN2C) in sporadic pancreatic endocrine tumors argues against tumor-suppressor function.
abstract: Pancreatic endocrine tumors (PETs) arise sporadically or are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome or von Hippel-Lindau syndrome. About 90% of patients with familial MEN1 display detectable MEN1 gene (menin) mutations. The cyclin-dependent kinase inhibitor p27 (CDKN1B) is a downstream target of menin and has been recently shown to be responsible for the multiple endocrine neoplasia-like syndrome in rats, where affected animals develop multiple tumors and hyperplasia in endocrine tissues, including the pancreatic islets of Langerhans. A germline nonsense truncation mutation of p27 has been recently described in a suspected MEN1 family without MEN1 mutation, raising the possibility that p27 mutation could be responsible for MEN1 phenotype. Somatic MEN1 mutations occur at low frequency in sporadic PETs; here, we subjected p27 to mutational analysis in 27 sporadic PETs. As an additional menin target, analysis of the p18 (CDKN2C) gene was included. In the p27 gene, one common polymorphism (V109G) and one novel polymorphism (g/a) in the noncoding part of exon 2 were identified. Three known polymorphisms were found in the p18 gene. These data suggest that p27 and p18 are unlikely to present classic tumor-suppressor genes in sporadic PETs.
authors: Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, Uppsala, Sweden.
authors: Daniel
authors: D
authors: Lindberg
authors: Göran
authors: G
authors: Akerström
authors: Gunnar
authors: G
authors: Westin
mesh_terms: D018389:Codon, Nonsense / Q000235:genetics; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007340:Insulinoma / Q000235:genetics*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D050763:Cyclin-Dependent Kinase Inhibitor p18; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27
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