PATERNALLY DERIVED H19 IS DIFFERENTIALLY EXPRESSED IN MALIGNANT AND NONMALIGNANT TROPHOBLAST

The paternal allele of the H19 gene has been shown to be transcription ally inactive in the developing human embryo. Using reverse transcript ion PCR and RNase protection assays, we demonstrate that expression of H19 is predominantly, but not exclusively, from the maternal allele i n the human placenta. In situ hybridization analysis shows strong expr ession of the H19 gene in eight complete hydatidiform moles, hyperplas tic tissues consisting of trophoblasts which contain only paternally d erived genetic material, indicating that H19 is not functionally impri nted in this tissue. H19, a putative growth suppressor, is oppositely imprinted to the neighboring insulin-like growth factor II (IGF2) gene and an up-regulation of IGF2 expression has been linked previously to a down-regulation of H19 expression in the progression to Wilms' tumo r. Two cases of complete hydatidiform mole which progressed to chorioc arcinoma show high levels of expression of both H19 and IGF2. The chor iocarcinomas which developed from these complete hydatiform moles show ed similar expression of IGF2 but a decreased number of H19-positive c ells, which may reflect selection for cells expressing IGF2 and agains t those expressing H19 in this tissue.