[A study for the genesis of trophoblastic tumor, with reference to its androgenetic origin]

Complete mole is an abnormal human pregnancy which is characterized by grossly swollen villi in the absence of a fetus. It has been widely accepted that of all forms of pregnancy that leads to choriocarcinoma, the risk associated with moles is by far the highest, being 2000 to 4000 times greater than that of normal pregnancy or abortion (1). However there has been no direct proof that choriocarcinoma indeed derives from complete mole. In the present study, to shed some light on the genesis of trophoblastic tumor, chromosome, HLA and PGM1 polymorphisms were examined for complete moles and choriocarcinomas. As a result, it has been ascertained that complete mole was androgenetic in origin; the entire genome of the molar conceptus was paternally derived. More than ninety percent of cases were resulted from fertilization of an empty egg (i.e. the nucleus was either eliminated or inactivated) by a haploid sperm. The paternally derived haploid set then duplicated without cytokinesis and restored diploidy. This class of moles had invariably a 46, XX karyotype and was completely homozygous for any genetic markers. Fertilization of an empty egg by two spermatozoa could elucidate remaining cases. The androgenetic origin of complete mole has provided us with a means to directly evaluate the relationship between choriocarcinomas and their putative forerunners; complete homozygosity and exclusive inheritance of a paternal genome would be expected if the tumor arose from complete mole derived from the former mechanism. However, the heterozygosity observed in choriocarcinoma cells suggested that the tumor did not arise from moles which originated from the fertilization of an empty egg by a haploid sperm.(ABSTRACT TRUNCATED AT 250 WORDS)