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Study sheds new light on role of genetic mutations in colon cancer development
Date:6/7/2012

ondrial DNA from normal and cancerous colon tissue resected from 20 patients prior to chemotherapy.

Bielas and colleagues first set out to analyze mutation rates in mitochondrial DNA because they wanted to see if it could act as a surrogate for nuclear DNA as a cancer biomarker. "Cells contain a thousandfold more mitochondrial genetic material than nuclear DNA, so theoretically you'd need a thousand times less tissue to get the same genetic information to predict clinical outcomes such as how fast a tumor would progress or whether it would be resistant to therapy," Bielas said.

While mitochondrial DNA proved to be an unreliable stand-in for nuclear DNA as a cancer biomarker, it offers promise as a new drug target.

"If we could increase DNA damage and mutation within the mitochondrial genome, theoretically we could decrease cancer," Bielas said. "That's what we're testing now. This is a whole new hypothesis."

The way mitochondria maintain genetic stability in the face of cancer, Bielas suggests, may be because unlike normal cells, cancer cells do not need oxygen to survive. In fact, cancer cells decrease the process by which they get energy from the mitochondria and rely instead on a process called glycolysis, which is a form of energy production in the absence of oxygen.

"We believe less damage occurs to mitochondrial DNA of cancer cells because they no longer need oxygen," he said. "If we could program a cancer cell to once again need oxygen, we expect it would die with minimal side effects."

Bielas and colleagues are now testing this theory in the laboratory, seeing whether cancer cells that are reprogrammed to utilize oxygen and/or are targeted for mitochondrial DNA damage respond better to certain therapeutic agents.

"This finding is a game-changer because it challenges previous notions about the role of mutations in cancer development," said Bielas, who is also an affiliate assistant professor of pathology at the University of Washi
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Contact: Kristen Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center
Source:Eurekalert

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