Cell Surprise: Mutation In Cancer Cells
(Ivanhoe Newswire) --A game-changing find challenges previously held beliefs about the role of mutations in cancer development. Researchers at the Fred Hutchinson Cancer Research Center in Seattle say their findings show that the number of new mutations is significantly lower in cancers than in normal cells.
"This is completely opposite of what we see in nuclear DNA, which has an increased overall mutation burden in cancer," cancer geneticist Jason Bielas, Ph.D., an assistant member of the Public Health Sciences and Human Biology divisions at the Hutchinson Center was quoted as saying.
Mitochondria, which are primarily responsible for the cell's energy production, have their own set of DNA, which encodes genes critical for the functioning of the cell. While the role of genomic instability has been well characterized in nuclear DNA, this is the first attempt to determine whether instability in mitochondrial DNA may play a similar role in cancer growth and metastasis.
"We were surprised to find that the frequency of new mutations in mitochondrial DNA from tumor cells is decreased compared to that of normal cells," Dr. Bielas was quoted as saying. “By extension, this suggests, somewhat counter intuitively, that higher mitochondrial mutation rates may actually serve as a barrier to cancer development, and drugs that focus directly on increasing mitochondrial DNA damage and mutation might swap cancer's immortality for accelerated aging and tumor-cell death."
Dr. Bielas suggests that the mitochondria are able to maintain genetic stability in the face of cancer 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 glycolysis, 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," Dr. Belias added. "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 currently testing this theory in the lab, 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 work started with the idea that there would be a huge mutation burden in the mitochondrial DNA, but our findings were completely opposite of what we had expected. Hopefully our discovery will open up new avenues for treatment, early detection and monitoring treatment response of colon cancer and other malignancies," Dr. Bielas concluded
SOURCE: PLoS Genetics, June 7