Mutational Analysis of p27 (CDKN1 B) and p18 (CDKN2C) in Sporadic Pancreatic Endocrine Tumors Argues against Tumor-Suppressor Function

Neoplasia: An International Journal for Oncology Research

关键词: cyclin-dependent kinase inhibitor;    p27Kip1;    p181NK4C;    sporadic pancreatic endocrine tumors;    tumor-suppressor gene;   

DOI  :  10.1593/neo.07328

来源: DOAJ

【 摘 要 】

Pancreatic endocrine tumors (PETs) arise sporadically or are associated with multiple endocrine neoplasia type 1 (MENi) syndrome or von Hippel-Lindau syndrome. About 90% of patients with familial MENi display detectable MEN1 gene (menin) mutations. The cyclin-dependent kinase inhibitor p27 (CDKN1 B) 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 MENi family without MENi mutation, raising the possibility that p27 mutation could be responsible for MENi phenotype. Somatic MENi 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 (V1 09G) 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.

【 授权许可】

Unknown