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Cancer Begins With Epigenetic Changes: Study

In a new study that is to appear in the January issue of Nature Reviews Genetics, a Johns Hopkins researcher suggests that cancers might begin with epigenetic //alterations instead of the traditional view that cancers usually occur in individuals whose genes have been altered by prevailing conditions. "We're not contradicting the view that genetic changes occur in the development of cancers, but there also are epigenetic changes and those come first," said lead author Andrew Feinberg, M.D., M.P.H., King Fahd Professor of Medicine and director of the Center for Epigenetics in Common Human Disease at Johns Hopkins.

His views are supported by fellow researchers in Sweden and at Fred Hutchinson Cancer Research Center. Professor Feinberg said that cells that have undergone epigenetic changes do not exhibit any alterations under the microscope, but subtle changes are detected at the level of the genome. Doctors can treat patients who are harboring these changes in much the same way as a cardiologist prescribes "cholesterol-lowering drugs to patients with fat deposits in their arteries," to prevent heart attacks. Epigenetic changes have been implicated in the development of cancer, birth defects and psychiatric conditions in previous studies. These changes include switching off the protection mechanisms that prevent the development of cancer. Cancers develop in three steps according to this study. The first step is where the epigenetic changes alter the balance in favor of the tumor-progenitor cells, secondly these cells trigger a mutation in the disturbed cells. As an example the altered sequence of chromosomes in chronic myeloid leukemia is mentioned. Finally, there is increased genetic and epigenetic instability leading to formation of the tumors. "Greater attention should be paid to the apparently normal cells of patients with cancer or those at risk for cancer, as they might be crucial targets for epigenetic alteration and might be an important target for pr evention and screening," Feinberg concluded.

Andrew Feinberg of Johns Hopkins; Rolf Ohlsson of Uppsala University, Sweden; and Steven Henikoff of the Howard Hughes Medical Institute at the Fred Hutchinson Cancer Research Center are the authors of the paper which can be read at nature.com/nrg/journal/v7/n1/full/nrg1748.html

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