The state of the p53 gene in human papillomavirus (HPV)-positive and HPV-negative genital precancer lesions and carcinomas as determined by single-strand conformation polymorphism analysis and sequencing.
Human papillomavirus (HPV) is frequently associated with cervical carcinoma. Inactivation of the p53 tumor suppressor gene product by binding to the HPV encoded E6 protein is considered as an important pathway for malignant progress in HPV-infected cells. In contrast, mutations of the p53 gene have been found in HPV-negative cervical carcinoma cells. To evaluate the involvement of p53 inactivation for the development of genital carcinoma, we determined the state of the p53 gene in 20 genital precancer lesions and carcinomas, which had been previously studied for the expression of p53 protein and the presence of HPV DNA. Exons 5 through 9 of the p53 gene were analyzed by single-strand conformation polymorphism analysis of polymerase chain reaction (PCR)-amplified DNA fragments, and the results obtained by the PCR-SSCP analysis were confirmed by DNA sequencing. No mutations were detected in any of the specimens, including the three HPV-negative cases. The present results 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 participate in genital carcinogenesis.
Kurvinen
K
K
Department of Pathology, University of Kuopio, Finland.
Tervahauta
A
A
Syrjänen
S
S
Chang
F
F
Syrjänen
K
K
D001483:Base Sequence; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004277:DNA, Single-Stranded / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics* / Q000821:virology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology*; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology*
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53