DNA methylation and genetic instability in colorectal cancer cells

DNA methylation and genetic instability in colorectal cancer cells

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

Abstract

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.

Footnotes

↵ * To whom reprint requests should be addressed.
Bert Vogelstein
ABBREVIATIONS:

5-aza-C,

5-azacytidine;

β-gal,

β-galactosidase;

X-Gal,

5-bromo-4-chloro-3-indolyl β-d-galactopyranoside;

LTR,

long terminal repeat, MMR, mismatch repair