Inactivation of tumor suppressor genes in uterine cervix carginogenesis

The importance of inactivation of tumor suppressor genes in the development /progression of carcinomas of the uterine cervix is reviewed. It is well kn own that HPV-related oncogenes are strongly linked to cervical cancer. Howe ver, fewer studies have explored the occurrence of inactivation of tumor su ppressor genes in this neoplasia. Genetic deletions affecting tumor suppres sor genes are the most common mechanism of inactivation of these genes. Stu dies using conventional molecular techniques such as restriction fragment l ength polymorphism (RFLP) and Southern Blot showed how frequency of deletio ns in cervical carcinomas. Detection of deletions by using RFLP and Souther n Blot prevents several disadvantages, the most important being the difficu lty in analyzing pure tumor cells. More sensitive approaches include tissue microdissection and PCR analysis of microsatellites. Using these approache s, it has been shown that genetic deletions are, in fact, frequent events i n cervical cancers, being detected in up to 95% of the cases. Multiple gene tic loci are involved, including chromosomes 3p, 5p, 6p and 11q. Deletions are detected even in precursor lesions (cervical intraepithelial neoplasia, CIN). Some deletions have been correlated with prognostic parameters, such as stage, depth of invasion, and vascular space involvement. It is conclud ed that cervical carcinogenesis, like in other tumors, is a multistep proce ss, characterized by the accumulation of events including activation of onc ogenes, as well as inactivation of tumor suppressor genes.