Chromosome and cellular origin of choriocarcinoma.

The preferential association of choriocarcinoma with complete moles has long been recognized. In fact, of all forms of pregnancy that lead to choriocarcinoma, the risk associated with hydatidiform moles is 2000 to 4000 times greater than that of normal pregnancy or abortion. In order to corroborate the cell lineage between hydatidiform moles and choriocarcinoma, we investigated the chromosomal constitution and polymorphisms in the latter cells. Three choriocarcinomas from three women with a previous history of hydatidiform moles were examined chromosomally. Two hundred thirteen cells were analyzed for their chromosome number by conventional Giemsa staining; karyotyping of 33 cells with Q- and C-banding revealed 13 kinds of structural abnormalities unequivocally identified as of clonal origin. Two cases exhibited involvement of the long arm of chromosome 1 in rearrangements. Complete homozygosity and exclusive inheritance of a paternal genome would be expected if the tumor arose from a preceding molar pregnancy. However, the heterozygosity observed in choriocarcinoma cells suggests no common cellular lineage with complete moles; the latter originate through fertilization of an "empty egg" by a haploid sperm, followed by duplication of the chromosomes. Several possibilities have to be considered for the origin of choriocarcinomas, since it seems unlikely that alterations in the paracentric areas of the marker chromosomes occurred during tumor development. One possibility is that moles which are characterized by heterozygosity may transform into choriocarcinomas. Another possibility is that such tumors may originate from trophoblasts of the conceptuses rather than from moles.