Mutational analysis of the p27kip1 gene in hepatocellular carcinoma

p27Kip1 is an inhibitor of cyclin-dependent kinase. It has been reported that reduced p27Kip1 expression is present in human hepatocellular carcinoma. To determine the role of p27Kip1 in hepatocarcinogenesis, 46 cases with hepatocellular carcinomas were studied. p27Kip1 mutation was first screened by single strand conformation polymorphism, and direct DNA sequencing was then performed on those cases 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 identified at codon 55 (GCG→GCA) in six of the 46 cases. However, the polymorphism at codon 55 was also present in seven of 93 healthy controls (7.5%), indicating that it is not associated with a predisposition for development of hepatocellular carcinoma (Fisherʹs exact test, P>0.05). These results show that p27Kip1 mutation is not a frequent event in human hepatocellular carcinoma, and suggest that it may be inactivated predominantly by transcriptional and/or posttranscriptional regulation rather than genomic aberrations.