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'-deoxycytidine, a specific inhibitor of cytosine DNA methyltransferase. Treated cells showed several significant and reproducible changes. (a) Equal expression of maternal and paternal alleles of insulin-like growth factor 2 switched to predominant expression of a single parental allele. (b) H19 expression was reactivated. (c) Biallelic H19 expression switched to monoallelic expression. (d) 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-aza-2'-deoxycytidine on tumor cells with loss of imprinting is not random but specific to one allele.
Barletta
J M
JM
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Rainier
S
S
Feinberg
A P
AP
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D018392:Genomic Imprinting / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014407:Tumor Cells, Cultured
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine