Genetics and molecular markers in gestational trophoblastic disease with special reference to their clinical application

Gestational trophoblastic disease (GTD) encompasses a diverse group of lesions with specific cytogenetic and molecular pathogenesis. Although cytogenetic studies have been extensively reported, the molecular pathogenesis is poorly understood. We will summarize some of the recent molecular observations and correlate them with the pathology of GTD. Complete mole is androgenetic in origin. Thus, if a monoallelic contribution can be shown in complete mole, this would render the gene susceptible to functional inactivation by ‘one-hit’ kinetics. Alternatively, uniparental transmission of genes that are subject to parental imprinting in humans would impair their regulation. Loss of NECC1 expression, biallelic deletions at the critical (7p12-7q11.23) region and enhanced H19 expression in choriocarcinoma would reflect the genetic features exhibited by the putative forerunner, complete mole. In addition to the unique genetic features shown in GTD, alterations in gene expression profiles accompanied by malignant conversion of trophoblasts would facilitate the development of choriocarcinogenesis from complete mole. With recent advances in molecular techniques, further work is still necessary to provide a better understanding and useful markers for persistent trophoblastic disease. These may provide useful prognostic indications that may guide the different diagnosis of GTD.