REVERSAL OF LOSS OF IMPRINTING IN TUMOR-CELLS BY 5-AZA-2'-DEOXYCYTIDINE

To determine whether loss of imprinting in cancer might be reversed by altering DNA methylation, we treated tumor cells with 5-aza-2'-deoxyc ytidine, a specific inhibitor of cytosine DNA methyltransferase, Treat ed cells showed several significant and reproducible changes, (a) Equa l expression of maternal and paternal alleles of insulin-like growth f actor 2 switched to predominant expression of a single parental allele , (b) H19 expression was reactivated, (c) Biallelic H19 expression swi tched La mono-allelic expression, (d) Biallelic methylation of H19 swi tched to preferential allelic methylation, These results imply that ab normally imprinted cells susceptible to epigenetic modification and th at the effect of 5-aza-2'-deoxycytidine on tumor cells with Boss of im printing is not random hut specific to one allele.