Genetic lesion in the carcinogenesis of cervical cancer

Allelic loss at specific chromosomal loci was demonstrated in carcinoma of the cervix (CaCx) obtained from Hong Kong Chinese by restriction fragment length polymorphism analysis. Altogether 12 patients with CaCx, 7 with cervical intraepithelial neoplasia (CIN) and 7 with normal cervical tissues were studied. Polymorphic DNA markers for chromosome 3 were used and the tumour and constitutional genotypes of the above patients were compared. Loss of heterozygosity (LOH) was found in 10 out of 12 informative cases with CaCx at RAF-1 locus (3p25) and in 10 out of 11 cases at D3S3 (3p14). Further study on patients with cervical intraepithelial neoplasia showed LOH at both 3p25 and 3p14 in four out of five cases. In normal cervical tissues, no LOH was demonstrated at both loci. Our data suggest that the deletion events occurring on the short arm of chromosome 3 at 3p25 and 3p14 are early events in the development of carcinoma of cervix. Since recessive genes have been reported to reside within or close to these 2 loci, important genes may have been lost or inactivated in the genesis of this tumour. Moreover, human papillomavirus (HPV) type 16, 18 or 33 was found in 8/12 of the carcinomas and 4/7 of CIN using Polymerase Chain Reaction and/or Southern Blot hybridization, confirming the close association with human papillomavirus. Whether the observed genetic lesions in the short arm of chromosome 3 in cervical "premalignant" and malignant lesions and their consistent association with high risk HPV represent independent events in the development of carcinoma of cervix will be discussed.