RELAXATION OF IMPRINTING IN TROPHOBLASTIC DISEASE

Genomic imprinting-the uniparental-dependent transmittance of a geneti c trait-has been accepted in recent years as a major mechanism in mamm alian genetics. We studied the expression of the H19 gene, a parentall y imprinted (maternally expressed) gene, by in situ hybridization in h uman placenta and trophoblastic disease. Expression was found to be ab undant, in a decreasing order, in the intermediate trophoblast (villou s and interstitial), the cytotrophoblast, and the syncytiotrophoblast. The villous stroma was also prominently labeled. Partial hydatidiform mole showed a similar pattern of expression as normal placenta. As ex pected, complete hydatidiform mole, whose genome consists of two haplo id sets of paternal origin, was not labeled in the villous stroma and surrounding trophoblastic layer. However, some of the large mononuclea r cells in the proliferating groups sprouting from the villous surface were strongly labeled. Prominent expression of H19 was found in place ntal site trophoblastic tumor and gestational choriocarcinoma. The phe nomenon of emergence of expression of alleles subject to repression ac cording to their gamete of origin is termed relaxation of imprinting, and is considered to be relevant to tumorigenesis. We suggest that the expression of the maternally expressed H19 gene in the androgenetic t issue of complete hydatidiform mole represents relaxation of imprintin g and may be associated with its malignant potential. (C) 1994 Academi c Press, Inc.