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Proc. Natl. Acad. Sci. USA
Vol. 94, pp. 2545-2550, March 1997
Medical Sciences

DNA methylation and genetic instability in colorectal cancer cells

Christoph Lengauer, Kenneth W. Kinzler, and Bert Vogelstein

Howard Hughes Medical Institute at The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231

Contributed by Bert Vogelstein, December 31, 1996

Apparent alterations in DNA methylation have been observed in many cancers, but whether such alterations represent a persistent alteration in the normal methylation process is not known. In this study, we report a striking difference in the expression of exogenously introduced retroviral genes in various colorectal cancer cell lines. Extinguished expression was associated with DNA methylation and could be reversed by treatment with the demethylating agent 5-azacytidine. A striking correlation between genetic instability and methylation capacity suggested that methylation abnormalities may play a role in chromosome segregation processes in cancer cells.


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