Cytogenetics of trophoblasts from complete hydatidiform moles

The risk of developing choriocarcinoma following a complete hydatidiform mole (CHM) is 2000-4000 times greater than the risk following a normal pregnancy. To understand more fully the increased susceptibility of the molar trophoblast to malignant transformation, we separated the trophoblastic cells from the stromal cells in 14 complete moles and cultured them for cytogenetic analysis. The numerical and structural abnormalities found were compared with those found in the trophoblasts from normal pregnancy and malignant choriocarcinoma cell lines. The percentage of polyploid cells was 2.8 times greater in molar trophoblasts than in normal trophoblasts. Although we found no consistent chromosomal abnormality in the molar trophoblasts, these cells were significantly more vulnerable to chromosomal breakage than the molar fibroblasts, normal trophoblasts, normal fibroblasts, and maternal decidual cells. Out of a total of 103 breakpoints observed in 338 cells, 42 coincided with known fragile sites, 18 with the location of protooncogenes, 27 with breakpoints reported in other neoplasia, and 18 with breakpoints found in four choriocarcinoma cell lines. The chromosomes in choriocarcinoma cell lines have hypotetraploid mode and many structural rearrangements. Our results suggest that the genetic instability found in the molar trophoblasts may be responsible for progressive karyotypic changes and greater susceptibility to malignant transformation.