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In lung cancer, silencing one crucial gene disrupts normal functioning of genome
Date:12/30/2008

PHILADELPHIA While examining patterns of DNA modification in lung cancer, a team of international researchers has discovered what they say is a surprising new mechanism. They say that "silencing" of a single gene in lung cancer led to a general impairment in genome-wide changes in cells, contributing to cancer development and progression.

In the January 1, 2009, issue of Cancer Research, a journal of the American Association for Cancer Research, they also report finding a strong link between modification of the key gene, MTHFR, and tobacco use by lung cancer patients even if the patient had smoked for a short period of time.

The findings reinforce tobacco's link to lung cancer development, but show that deactivating one specific gene through a process known as hypermethylation causes systemic dysfunction, or hypomethylation, in many genes, said the study's senior investigator, Zdenko Herceg, Ph.D., head of the Epigenetics Group at the International Agency for Research on Cancer (IARC).

"We found that tobacco-mediated hypermethylation of MTHFR, and consequent partial or complete silencing of the gene, may trigger global hypomethylation and deregulation of DNA synthesis, both of which may contribute to cancer development," he said.

This methylation process, which involves chemically modifying normal DNA in order to change its activity, is seen as an increasingly important factor contributing to so-called "epigenetic inheritance" in cancer development, Herceg said. An epigenetic event is when non-genetic factors cause a gene to change its expression, and this is different from cancer caused by mutated genes that produce errant protein.

"Tobacco smoke contains many carcinogens, most of which are believed to cause genome damage," he said. "While there is evidence that the mutations induced by these tobacco carcinogens do play an important role in cancer development, our study reveals the novel and surprising r
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Contact: Jeremy Moore
Jeremy.moore@aacr.org
267-646-0557
American Association for Cancer Research
Source:Eurekalert

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