THE STATE OF THE P53 GENE IN HUMAN PAPILLOMAVIRUS (HPV)-POSITIVE AND HPV-NEGATIVE GENITAL PRECANCER LESIONS AND CARCINOMAS AS DETERMINED BYSINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS AND SEQUENCING

Human papillomavirus (HPV) is frequently associated with cervical carc inoma. Inactivation of the p53 tumor suppressor gene product by bindin g to the HPV encoded E6 protein is considered as an important pathway for malignant progress in HPV-infected cells. In contrast, mutations o f the p53 gene have been found in HPV-negative cervical carcinoma cell s. To evaluate the involvement of p53 inactivation for the development of genital carcinoma, we determined the state of the p53 gene in 20 g enital precancer lesions and carcinomas, which had been previously stu died for the expression of p53 protein and the presence of HPV DNA. Ex ons 5 through 9 of the p53 gene were analyzed by single-strand conform ation polymorphism analysis of polymerase chain reaction (PCR)-amplifi ed DNA fragments, and the results obtained by the PCR-SSCP analysis we re confirmed by DNA sequencing. No mutations were detected in any of t he specimens, including the three HPV-negative cases. The present resu lts suggest that the functional inactivation of p53 is not invariably required for the induction of malignant transformation in the genital tract, and thus other genetic events can also significantly participat e in genital carcinogenesis.