[Inactivation of tumor suppressor genes in uterine cervix carcinogenesis]

The importance of inactivation of tumor suppressor genes in the development/progression of carcinomas of the uterine cervix is reviewed. It is well known that HPV-related oncogenes are strongly linked to cervical cancer. However, fewer studies have explored the occurrence of inactivation of tumor suppressor genes in this neoplasia. Genetic deletions affecting tumor suppressor genes are the most common mechanism of inactivation of these genes. Studies using conventional molecular techniques such as restriction fragment length polymorphism (RFLP) and Southern Blot showed low frequency of deletions in cervical carcinomas. Detection of deletions by using RFLP and Southern Blot presents several disadvantages, the most important being the difficulty in analyzing pure tumor cells. More sensitive approaches include tissue microdissection and PCR analysis of micro-satellites. Using these approaches, it has been shown that genetic deletions are, in fact, frequent events in cervical cancers, being detected in up to 95% of the cases. Multiple genetic 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 concluded that cervical carcinogenesis, like in other tumors, is a multistep process, characterized by the accumulation of events including activation of oncogenes, as well as inactivation of tumor suppressor genes.