Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour
- Resource Type
- Authors
- Marja Steenman; Andrew P. Feinberg; Isabelle L. Horon; Craig J. Dobry; Paul E. Grundy; Shirley Rainier
- Source
- Nature genetics. 7(3)
- Subject
- Male
endocrine system diseases
Tumor suppressor gene
Transcription, Genetic
Biology
Methylation
Wilms Tumor
Loss of heterozygosity
Embryonic and Fetal Development
Genomic Imprinting
Insulin-Like Growth Factor II
Genetics
medicine
Humans
Genes, Tumor Suppressor
RNA, Messenger
RNA, Neoplasm
Imprinting (psychology)
Promoter Regions, Genetic
Regulation of gene expression
Wilms' tumor
DNA, Neoplasm
medicine.disease
female genital diseases and pregnancy complications
Kidney Neoplasms
Gene Expression Regulation, Neoplastic
Genes
Organ Specificity
embryonic structures
DNA methylation
Cancer research
Female
Genomic imprinting
- Language
- ISSN
- 1061-4036
The insulin-like growth factor-II (IGF2) and H19 genes are imprinted in mouse and human, with expression of the paternal IGF2 and maternal H19 alleles. IGF2 undergoes loss of imprinting (LOI) in most Wilms' tumours (WT). We now show that: (i) LOI of IGF2 is associated with a 80-fold down regulation of H19 expression; (ii) these changes are associated with alterations in parental-origin-specific, tissue-independent sites of DNA methylation in the H19 promoter; and (iii) loss of heterozygosity is also associated with loss of H19 expression. Thus, imprinting of a large domain of the maternal chromosome results in a reversal to a paternal epigenotype. These data also suggest an epigenetic mechanism for inactivation of H19 as a tumour suppressor gene.