The role of p53 inactivation in human cervical cell carcinoma development.
We investigated the association between human papillomavirus (HPV) infection and p53 gene mutation in 47 primary uterine cervical cancers. HPV DNA sequences were present in 43 cancers (91.5%), and one of these cancers contained a p53 gene mutation. In addition, one of the remaining four HPV-negative cancers also contained a p53 gene mutation. As a result, p53 inactivation corresponded to the development of 44 of the primary uterine cervical cancers studied (93.6%). We obtained both primary and recurrent tumours from four cases. In two of these cases, the HPV genomes that were present in an episomal state in the primary tumours were observed to have disappeared in the recurrent tumours. One of these recurrent tumours also contained a p53 gene mutation, which suggested the possibility that p53 inactivation was required in order to maintain the aggressive behaviour in this cancer either by an HPV infection or by a p53 gene mutation. No MDM2 gene amplification was observed in the tumours that carried neither HPV DNAs nor p53 gene mutations.
Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Japan.
K
K
Miwa
S
S
Miyamoto
H
H
Kato
T
T
Imamura
M
M
Nishida
Y
Y
Yoshikawa
Y
Y
Nagata
N
N
Wake
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000821:virology; D001483:Base Sequence; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral / Q000235:genetics; D003043:Cocarcinogenesis; D004252:DNA Mutational Analysis; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000821:virology; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral / Q000502:physiology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D014412:Tumor Virus Infections / Q000235:genetics* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
D015344:DNA Probes, HPV; D004279:DNA, Viral; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2