Mutational analysis of the p27(kip1) gene in hepatocellular carcinoma

p27(Kip1) is an inhibitor of cyclin-dependent kinase. It has been reported that reduced p27(Kip1) expression is present in human hepatocellular carcin oma. To determine the role of p27(Kip1) in hepatocarcinogenesis, 46 cases w ith hepatocellular carcinomas were studied. p27(Kip1) mutation was first sc reened by single strand conformation polymorphism. and direct DNA sequencin g was then performed on those casts with mobility shifts. Two polymorphism sites were found. One is a previously described polymorphism at codon 109 ( GTC --> GGC) which was found in two cases. The second polymorphism was iden tified at codon 55 (GCG --> GCA) in six of the 46 cases. However. the polym orphism at codon 55 was also present in seven of 93 healthy controls (7.5%) . indicating that it is not associated with a predisposition for developmen t of hepatocellular carcinoma (Fishers exact test, P > 0.05). These results show that p27(Kip1) mutation is not a frequent event in human hepatocellul ar carcinoma. and suggest that it may be inactivated predominantly by trans criptional and/or posttranscriptional regulation rather than genomic aberra tions. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.