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Whitehead Study Establishes Role Of DNA Methylation In The Stability Of DNA,,,Suggests Possible Role Of Undermethylation In Cancer

Scientists at the Whitehead Institute for Biomedical Research have established for the first time that DNA methylation, a chemical process by which cells alter how genes are read without changing the basic text, may also be responsible for maintaining the integrity of the genome, or in other words, for ensuring that the 3 billion-letter DNA code is copied accurately when cells divide.

The findings, reported in the September 3 issue of Nature, have implications for better understanding the molecular origins of cancer. These findings suggest that the early cancer cell may use reduced DNA methylation to decrease genome stability and increase the mutation rate, both of which are crucial for the development of malignant disease. The findings resolve contradictory results from previous research on the connection between methylation and cancer.

"One of the earliest hallmarks of cancer is the decreased stability of the cellular DNA, which causes genome rearrangements and mutations and sets the stage for the cell to develop malignant disease," says Dr. Rudolf Jaenisch, Member of the Whitehead Institute and senior author on this study.

"Previously, some scientists found that tumor cells exhibited diminished methylation, while others have found excess methylation. Excess methylation was linked to the silencing of tumor suppressor genes, whereas the role of diminished DNA methylation in the malignant process was obscure. Our present study shows that reduced methylation may be responsible for the decrease in genomic stability, and therefore, the increase in mutations and chromosome loss seen in the early cancer cell," says Dr. Jaenisch.

In this study, first author Dr. Richard Chen and his colleagues in Dr. Jaenisch's lab studied cultured mouse cells lacking DNA methyltransferase (MTase), the enzyme responsible for methylating DNA. Mice carrying this mutation die in the womb. However, embryonic cells carrying t
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Contact: Seema Kumar
kumar@wi.mit.edu
(617) 258-6153
Whitehead Institute for Biomedical Research
2-Sep-1998


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