Expression, promoter usage and parental imprinting status of insulin-like growth factor II (IGF2) in human hepatoblastoma: uncoupling of IGF2 and H19 imprinting.

We have studied the promoter utilization and parental imprinting status of human IGF2 in three genetically informative hepatoblastomas from patients ranging in age from 9 months to 3 years. In all three cases, there is a downregulation of promoter P1 in the tumor tissues while the P2 and P3 promoters are upregulated compared to the normal liver. One of three patients displayed loss of imprinting (LOI) of IGF2 in the tumor tissue. We also investigated the expression of the H19 gene in all three cases and the methylation pattern in H19 from the patient with LOI of IGF2. The expression of H19 was greatly reduced in all tumors. Monoallelic H19 expression however, was retained even in the case which showed LOI of IGF2. Unlike the situation in Wilms' tumor, no differences in the methylation pattern between the normal liver and tumor tissues were observed in the H19 promoter or 3' region, using HpII analysis. We show here, that in contrast to the situation in Wilms' tumor, H19 expression is not a prerequisite for maintaining a monoallelic IGF2 expression.