In exploring the genetics of mitochondria（线粒体） -- the powerhouse of the cell -- researchers at Fred Hutchinson Cancer Research Center have stumbled upon a finding that challenges previously² held beliefs about the role of mutations in cancer development. For the first time, researchers have found that the number of new mutations are significantly lower in cancers than in normal cells.

"This is completely opposite of what we see in nuclear DNA⁴, which has an increased overall mutation³ burden in cancer," said cancer geneticist Jason Bielas, Ph.D., whose findings are published in the June 7 issue of PLoS Genetics.

Mutations are changes in the genetic¹ sequence of a cell's genome and can occur as a result of environmental exposure to viruses, radiation and certain chemicals, or due to spontaneous errors during cell division or DNA replication.

Mitochondria, which are primarily responsible for the cell's energy production, are semi-autonomous; similar to the nucleus⁵, they have their own set of DNA, which encodes genes⁶ 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（新陈代谢） .

"We were surprised to find that the frequency of new mutations in mitochondrial DNA from tumor⁷ cells is decreased compared to that of normal cells," said Bielas, an assistant member of the Public Health Sciences and Human Biology divisions at the Hutchinson Center. "By extension, this suggests, somewhat counterintuitively, that higher mitcochondrial mutation rates may actually serve as a barrier to cancer development, and drugs that focus directly on increasing mitochondrial DNA damage and mutation might swap⁸ cancer's immortality⁹ for accelerated aging and tumor-cell death."

For the study, the researchers used using an ultra-sensitive test to detect mutations in mitochondrial DNA from normal and cancerous colon¹⁰ tissue resected from 20 patients prior to chemotherapy.

Bielas and colleagues first set out to analyze¹¹ mutation rates in mitochondrial DNA because they wanted to see if it could act as a surrogate（代用品） 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 resistant¹² 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."