Embryonal tumors such as Wilms' tumor (WT), embryonal rhabdomyosarcoma (eRMS) and hepatoblastoma have been thought to have a common pathogenetic mechanism. H19 was found to be inactivated in WT and eRMS either by loss of heterozygosity or by hypermethylation of the maternal allele. We show here that the expression of the H19 gene is inactivated by maternal allelic loss or hypermethylation in 7 out of 8 "sporadic" hepatoblastomas. Furthermore, we analyzed expression of the IGF2 gene. Loss of imprinting of the IGF2 gene was detected and linked to inactivation of the H19 gene in 2 hepatoblastomas. However, 2 sporadic cases demonstrated monoallelic expression of the IGF2 gene with inactivation of the H19 gene. Our results suggest that H19 may play a role as a common imprinted tumor suppressor gene in "sporadic" hepatoblastomas but may at times work independently of IGF2 expression.
Child Child, Preschool