[Chiba Medical Society Award Review] Developmental mechanism of hydatidiform moles based on DNA polymorphism analysis

[ABSTRACT] Hydatidiform moles are abnormal villous diseases characterized by excessive trophoblast proliferation. They are classified into two categories: complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM), whose cytogenetic constitution is exceptional. Gestational trophoblastic neoplasia (GTN) can develop from both types of hydatidiform moles. The incidence of GTN is different between CHM and PHM. However, it is occasionally difficult to diagnose hydatidiform moles. Thus, we have continued to diagnose them using molecular cytogenetic procedures, such as short tandem repeat (STR) polymorphisms, to determine their critical diagnosis. Based on STR analysis of CHM and PHM, the incidence of GTN was 15% and 2%, respectively. Furthermore, single nucleotide polymorphism array analysis has been introduced into the molecular karyotyping of whole genomes. Single nucleotide polymorphism array analysis clarified that heterozygous androgenetic CHM is of dispermic origin, but not a diploid sperm. Additionally, we showed that one-third of heterozygous androgenetic CHM had trisomic chromosomes. The origins of the additional chromosomes were not only paternal but also maternal, although they should be androgenetic. Molecular karyotyping revealed a spermatogonium-derived complete hydatidiform mole. A distinct diagnosis of hydatidiform moles is important for management of hydatidiform moles. Molecular biological procedures could elucidate the mechanisms underlying the development of hydatidiform moles.