Presence of p53 mutation in human cervical carcinomas associated with HPV-33 infection

Abstract

In this present study, we report the mutation of the p53 gene in vivo in human primary carcinomas of cervix and cervical intraepithelial neoplasia (CIN). The association of the HPV subtypes with the tumors was determined by multiplex primer polymerase chain reaction (PCR) amplification. The mutation of the p53 gene was detected using PCR amplification of the p53 exons followed by SSCP (single strand conformation polymorphism) and DNA sequencing analysis. The p53 mutation was detected in two out of two HPV-33 positive carcinomas but was absent in the HPV-16/-18 positive carcinomas (0 out of 8 cases). The p53 mutation was also detected in one out of four HPV-negative cervical carcinomas. No mutation of the p53 gene was detected in the CIN specimens (0 out of 7 cases). The two mutations in the HPV-33 associated cervical carcinoma were detected at codon 273 (CGT to TGT; arginine to cysteine) and intron 5 (24 base pair downstream of the 3' end of exon 5). The p53 mutation at codon 273 has been previously reported in one of the HPV-negative cervical carcinoma cell line (C33A). Our results indicate that mutation of the p53 gene is not a common event in human cervical cancers (3/14), and may be related to the infection of HPV-16/18 in the tumor. However, mutation of the p53 gene was detected in cervical carcinomas associated with HPV-33 and may be an important genetic event in this subgroup of carcinomas.