title: p53 mutations in HPV-negative cervical carcinoma.
abstract: Human papillomavirus (HPV) infection has been strongly linked to the development of cervical carcinoma. Two viral oncoproteins, E6 and E7, produced by HPV, have been shown to immortalize primary human genital epithelial cells by interacting with the protein products of cellular tumor suppressor genes p53 and Rb, respectively. E6 binds to the cellular p53 protein promoting p53 degradation and inactivity. This mechanism has been suggested to contribute to the oncogenesis of HPV-positive anogenital cancers. In HPV-negative cervical carcinoma, p53 mutation is thought to be the possible mechanism of oncogenesis. We have studied 257 cervical carcinoma specimens for HPV infection by Southern blot analysis and polymerase chain reaction (PCR). Of 257 samples, 39 were HPV-negative. We have further studied 21 HPV-negative specimens for p53 mutations utilizing PCR amplification of genomic DNA followed by single-stranded conformation polymorphism (SSCP) analysis and DNA sequencing. We found only two missense point mutations of p53 gene. In summary, although inactivation of p53 mediated either by E6 or by mutations may be an important key step in the development of cervical carcinoma, our study suggests that other mechanisms may also be involved in development of cervical cancer.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine 90048.
authors.forename: D J
authors.initials: DJ
authors.lastname: Park
authors.forename: S P
authors.initials: SP
authors.lastname: Wilczynski
authors.forename: R L
authors.initials: RL
authors.lastname: Paquette
authors.forename: C W
authors.initials: CW
authors.lastname: Miller
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D027383:Papillomaviridae / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: D004279:DNA, Viral