Genetic changes outside nuclear DNA may trigger half of all cancers

Washington, Mar 25 (ANI): Johns Hopkins scientists have said that genetic changes outside nuclear DNA may lead to over fifty percent of all cancers.

Already, it is known that a process known as hypermethylation, which is a buildup of chemical bonds on certain cancer-promoting genes, can render cells cancerous by disrupting biological brakes on runaway growth.

And now, scientists have claimed that the reverse process - demethylation - which wipes off those chemical bonds may also trigger more than half of all cancers.

One potential consequence of the new research is that demethylating drugs now used to treat some cancers may actually cause new cancers as a side effect.

"It's much too early to say for certain, but some patients could be at risk for additional primary tumors, and we may find that they need a molecular profile of their cancer before starting demethylating therapy," said Joseph Califano, M.D., professor of otolaryngology-head and neck surgery and oncology at Johns Hopkins.

The findings, based on studies of normal and cancer cells from human mouth, nose and throat tissue, provide more evidence that important regulators of gene activity occur outside as well as inside DNA in a cell's nucleus.

"While cancer-causing and other mutations alter vital protein-making pathways by rewriting the gene's DNA code, epigenetic changes affect genes without changing the code itself. The new studies tell us that such changes occur not only when methyl groups bond to a gene's on-off switch, but also when they come unglued," said Califano.

He further said that sporadic reports of demethylation as a tool in activating cancer-promoting genes inspired them to develop a systematic way to discover these epigenetic changes and show how the process is linked to cancer.

For evidence, the researchers treated two cell lines from normal oral tissue with the demethylating drug 5-azacytidine and collected a list of genes that were activated as a result.

They used special silicon chips carrying pieces of genetic material that allow thousands of genes to be analysed at one time to locate genes activated by demethylation.

The list was cross-referenced with genes "turned on" in 49 head and neck cancer samples and 19 normal tissue samples.

Overall, researchers found 106 genes specific to head and neck cancer that were activated by the demethylation process.

"Some of the genes regulate growth, others metabolize sugars and some have already been linked to cancer development," said Califano.

The findings of the study appear in the latest issue of PLoS One. (ANI)