Genetic Events Associated With Choriocarcinogenesis.

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We investigated 1. genetic origin of choriocarcinoma, 2. association of IGF2 and H19 imprinting with choriocarcinoma and 3. location of tumor suppressor gene (s) on human chromosome 7.1. The genetic origin of 24 trophoblastic neoplasms was determined by using PCR polymorphisms. Based on pregnancy history, the tumor included 9 postmolar trophoblastic tumors. Androgenetic origin was defined in 8 tumors, and the remaining one might have arisen from a normal fertilization. Six tumors retained genetic features carried by the homozygous complete mole. Two showed PCR polymorphisms compatible with that of the heterozygous complete mole. Our results support the suggestion that of all forms of pregnancy that predispose patients to choriocarcinoma, the most likely is the complete mole. Uniparental or monoallelic transmission of the genome that would render a particular type of tumor suppressor gene susceptible to functional inactivation may correspond to the propensity to malignancy in complete m … More ores. 2. We studied IGF2 and H19 expression, and methylation status of H19 in choriocarcinomas. Choriocarcinomas were characterized by a low expression of IGF2 and a high expression of H19. Biallelic expression of IGF2 or H19 was found frequently. Contrary to expectation, enhanced H19 expression was accompanied by hypermethylation of CpG sites over the entire gene region, apparently being at variance with the finding in normal placentae and androgenetic moles. The findings provide the possibility that the mutated promoter is responsible for overcoming transcriptional suppression by CpG methylation in the H19 gene. 3. To determine the chromosome carrying putative tumor suppressor gene (s), a single human chromosome was transferred into choriocarcinoma cells. Microcell-hybrids containing chromosome 7 were suppressed or modulated for tumorigenicity and exhibited altered in vitro growth properties, suggesting that chromosome 7 contains a putative tumor suppressor gene (s) for choriocarcinoma. In addition, we obtained evidence to define a critical region on chromosome 7 that was frequently lost in surgically removed choriocarcinoma tissues and cell lines. Using a panel of microsatellite markers, biallelic deletions were observed, which strongly suggests the presence of a tumor suppressor gene (s) within this critical region. Less