‘Silencing’ single gene in lung cancer disrupts genome functioning

December 31st, 2008 - 11:27 am ICT by IANS  

Washington, Dec 31 (IANS) “Silencing” a single gene in lung cancer disrupts functioning of genome in cancer cases, according to a new study.Researchers also found 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, who heads 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, said an IARC release.

“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 - role that silencing of normal genes plays in development of lung cancer,” he added.

The report will appear on Thursday’s issue of Cancer Research, a journal of the American Association for Cancer Research.

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