Analysis of Loss of Heterozygosity on the Chromosome 3, 4, 5 and 11 in Uterine Cervical Carcinomas

Nam, Jong Hee; Jung, Jong Jae; Choi, Chan

Abstract

Infection of cervical epithelial cells with specific human papilloma virus subtypes appears to be necessary etiological factors for most cervical carcinomas, but yet additional genetic changes such as activation of cellular proto-oncogenes and loss of tumor suppressor gene function seem to be required for progression to invasive carcinoma. Loss of heterozygosity analysis in a large sample is used to identify regions which harbor putative tumor suppressive genes since mutation of tumor suppressor genes is usually associated with remaining allelic loss and the deletion of normal alleles unmask mutated alleles. To investigate the incidence of loss of heterozygosity of 44 invasive squamous cell carcinomas of uterine cervix, we used polymerase chain reaction with 14 highly informative microsatellite markers located on the chromosome 3, 4, 5 and 11. The loss of heterozygosity at one or more markers was found in 16(36.3%) of 44 tumors examined. Of the 478 informative loci, 38(7.9%) LOH were detected. The chromosomal arms showing frequent LOH above the mean are 3q(12.9%), 11p (11.1%) and 11q(17.8%). Especially the locus D11S1986 mapped to 11q21-qter showed 22.8% LOH of 35 informative cases. These observations suggested that some putative tumor suppressor genes related to cervical carcinogenesis are located in the long arm of chromosome 11. Analysis of HPV infection by PCR showed positivity for HPV 16 or 18 in 28 cases(63.6%) of 44 cases examined. In group under the age of 50, the mean value of fractional allelic loss is higher in HPV infected cases. There is no any relationship between HPV infection and LOH pattern except some relation between HPV infection and allelic loss of 11q.