Study on p53 Mutation and MDM2 Amplification in Cervical Cancer

Chang, M K; Lee, S K; Jee, S G

Abstract

Mutation of the p53 tumor suppressor gene is one of the most commonly found genetic alteration in human cancer. The E6 gene product from human papillomavirus (HPV) 16 and 18 can inactivate the p53 protein by promoting its degradation via proteolytic ubiquitin system. But in HPV negative cervical carcinomas, many investigators have rarely found the p53 mutation. Still assuming that p53 inactivation is an essential step in development of HPV negative cervical cancer, alternative pathways have been discussed. MDM2 gene is a negative regulator of p53 protein activity, whereas p53 itself can stimulate MDM2 expression, thus forming a MDM2-p53 autoregulatory feedback loop. So, the author studied the presence of HPV-16/18 by PCR and the p53 mutation by PCR/SSCP and direct sequencing in 43 cases of primary cervical cancer. Furthermore, the author tried to define the MDM2 amplification by quantitative PCR, for evaluation of altenative pathway in p53 protein inactivation. In the results, the presence of HPV 16/18 were 32 cases and absence of HPV 16/18 were 11 cases.p53 mutations were shown in 8 cases. 4 cases were in HPV 16/18 positive cancers and the rest were in HPV-16/18 negative ones. Among the HPV-16/18 positive ones, there are three missence mutations at exon 6 and 7 and one frame shift mutations in exon 6. Among the in HPV-16/18 negative ones, there were two frame shift mutation in exon 5 and 7, one missence mutation in exon 8 and one deletion from exon 4 to 5. One amplification of the MDM2 gene was observed in HPV positive cervical cancers. According to this study results, it is rare to have p53 mutation or MDM2 amplification. The data shows that cervical cancer may be development in the p53 mutation and presence of HPV and in the absence of p53 mutation and HPV. So There may be additional mechanisms in the development of cervical cancer rather than p53 mutation and presence of HPV. For further clarification of the molecular mechanisms of cervical carcinogenesis,complete characterization of large number of tumor, possibly by automated technique, will be helpful.