Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour.
Nat Genet
; 7(3): 433-9, 1994 Jul.
Article
em En
| MEDLINE
| ID: mdl-7920665
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA de Neoplasias
/
RNA Mensageiro
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RNA Neoplásico
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Fator de Crescimento Insulin-Like II
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Regulação Neoplásica da Expressão Gênica
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Genes Supressores de Tumor
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Tumor de Wilms
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Impressão Genômica
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Neoplasias Renais
Limite:
Female
/
Humans
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Male
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
1994
Tipo de documento:
Article