Reversal of Loss of Imprinting in Tumor Cells by 5-aza-2"-deoycytidine

In order to determine whether loss of imprinting (LOI) in cancer might be reversed by altering DNA methylation, tumor cells were treated with 5-aza-2?deoxycytidine, a specific inhibitor of cytosine DNA methyltransferase. Treated cells showed several significant and reproducible changes: equal expression of maternal and paternal alleles of IGF2 switched to predominant expression of a single parental allele; H19 expression was reactivated; biallelic H19 expression switched to monoallelic expression; and biallelic methylation of H19 switched to preferential allelic methylation. These results imply that abnormally imprinted cells are susceptible to epigenetic modification, and that the effect of 5-azaCdR on tumor cells with LOI is not random but specific to one allele.

Inventor(s): Feinberg, Andrew Paul

Type of Offer: Licensing



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