Mutations of p53 and human papillomavirus infection in cervical carcinoma.
BACKGROUND
Oncogenic human papillomavirus (HPV) infection has been implicated in the pathogenesis of cervical carcinoma. The HPV oncoproteins E6 and E7 are though to play a crucial role in this process by their interactions with the p53 protein and the retinoblastoma susceptibility gene product, respectively. The E6 protein binds to and stimulates the degradation of the p53 protein. Mutations involving evolutionary conserved regions of the p53 gene also can alter p53 function. Point mutations of p53 frequently have been identified in a wide variety of human tumors.


METHODS
Forty-five cervical carcinoma samples were evaluated for the presence of mutations involving exons 5-8 of the p53 gene with polymerase chain reaction (PCR) amplification of genomic DNA, followed by single-stranded conformation polymorphism analysis and/or direct sequencing. The status of oncogenic HPV infection in the tumor tissues was analyzed by Southern blot and PCR.


RESULTS
Forty-two of 45 cervical carcinomas showed oncogenic HPV DNA: Of three HPV-negative samples, one harbored a missense point mutation of the p53 gene. An additional p53 point mutations was identified in a tumor with HPV 18 infection.


CONCLUSIONS
Oncogenic HPV DNA can be identified in most cervical carcinomas. Mutations involving conserved regions of p53, although infrequent in cervical cancer, occur preferentially in tumors without HPV infection. Inactivation of p53 function is important in the pathogenesis of cervical carcinoma.
Center for the Health Sciences, University of California, Los Angeles.
R L
RL
Paquette
Y Y
YY
Lee
S P
SP
Wilczynski
A
A
Karmakar
M
M
Kizaki
C W
CW
Miller
H P
HP
Koeffler
D000230:Adenocarcinoma / Q000235:genetics* / Q000382:microbiology; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000382:microbiology; D017124:Conserved Sequence; D015344:DNA Probes, HPV; D004273:DNA, Neoplasm / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D005784:Gene Amplification; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000382:microbiology
D015344:DNA Probes, HPV; D004273:DNA, Neoplasm; D004279:DNA, Viral