This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barletta, J. M. Articles by Feinberg, A. P. Search for Related Content PubMed PubMed Citation Articles by Barletta, J. M. Articles by Feinberg, A. P.

Reversal of Loss of Imprinting in Tumor Cells by 5-Aza-2'-deoxycytidine¹

Departments of Medicine [J. M. B., S. R., A. P. F.], Oncology [A. P. F.], and Molecular Biology & Genetics [A. P. F.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

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.

¹ This work was supported by NIH Grant CA65145.

² To whom requests for reprints should be addressed, at Center for Medical Genetics, Johns Hopkins University School of Medicine, 1064 Ross, 720 Rutland Avenue, Baltimore, MD 21205. Phone: (410) 614-3489; Fax: (410) 614-9819.

Received 9/17/96. Accepted 11/14/96.

This article has been cited by other articles:

				P. Onyango, S. Jiang, H. Uejima, M. J. Shamblott, J. D. Gearhart, H. Cui, and A. P. Feinberg Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages PNAS, August 6, 2002; 99(16): 10599 - 10604. [Abstract] [Full Text] [PDF]

				I. S. Pedersen, P. Dervan, A. McGoldrick, M. Harrison, F. Ponchel, V. Speirs, J. D. Isaacs, T. Gorey, and A. McCann Promoter switch: a novel mechanism causing biallelic PEG1/MEST expression in invasive breast cancer Hum. Mol. Genet., June 1, 2002; 11(12): 1449 - 1453. [Abstract] [Full Text] [PDF]

				Z.-H. Gao, S. Suppola, J. Liu, P. Heikkila, J. Janne, and R. Voutilainen Association of H19 Promoter Methylation with the Expression of H19 and IGF-II Genes in Adrenocortical Tumors J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1170 - 1176. [Abstract] [Full Text] [PDF]

				B. Chen, L. He, V. H. Savell, J. J. Jenkins, and D. M. Parham Inhibition of the Interferon-{{gamma}}/Signal Transducers and Activators of Transcription (STAT) Pathway by Hypermethylation at a STAT-binding Site in the p21WAF1 Promoter Region Cancer Res., June 1, 2000; 60(12): 3290 - 3298. [Abstract] [Full Text]

				S. Muller, D. van den Boom, D. Zirkel, H. Koster, F. Berthold, M. Schwab, M. Westphal, and W. Zumkeller Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors Hum. Mol. Genet., March 22, 2000; 9(5): 757 - 763. [Abstract] [Full Text] [PDF]

				I. S. Pedersen, P. A. Dervan, D. Broderick, M. Harrison, N. Miller, E. Delany, D. O'Shea, P. Costello, A. McGoldrick, G. Keating, et al. Frequent Loss of Imprinting of PEG1/MEST in Invasive Breast Cancer Cancer Res., November 1, 1999; 59(21): 5449 - 5451. [Abstract] [Full Text] [PDF]