High frequency of inactivation of the imprinted H19 gene in "sporadic" hepatoblastoma.
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.
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
R
R
Fukuzawa
A
A
Umezawa
K
K
Ochi
F
F
Urano
H
H
Ikeda
J
J
Hata
D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting / Q000235:genetics; D018197:Hepatoblastoma / Q000235:genetics*; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014314:Trisomy
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II