DETECTION OF RAS GENE-MUTATIONS AND HPV IN LESIONS OF THE HUMAN FEMALE REPRODUCTIVE-TRACT

Compatible with the epidemiology and natural history of cervical cance r and with experimental findings that HPV-immortalized nontumorigenic cells are similar to cervical carcinoma cells, in terms of the quantit y and type of viral RNA expressed, it is believed that additional cell ular genetic events are necessary for tumorigenic conversion. In the c urrent study we detected codon 12 point mutations of the K-ras oncogen e with an incidence of 28.2% in malignant lesions of the cervix, as we ll as HPV 1 8 at a higher rate than HPV16 (30.2% vs 27.9%) in genital lesions, by PCR and RFLP analysis. Codon 12 point mutations of K-, H- and N-ras were also found in benign lesions of the cervix, in endometr ial and in ovarian carcinomas, although at a lower frequency. It is su ggested that the mutationally activated ras oncogenes cooperate with H PV in the early stages of carcinogenesis of the human female reproduct ive tract.