Last year, mutations in mitochondrial DNA (mtDNA) were linked to development of the cancer. To investigate further, Anita Kloss-Brandstätter of Innsbruck Medical University, Austria, and colleagues compared the entire mitochondrial genome – some 16,569 base pairs – of cancerous and non-cancerous tissue from 30 men with prostate cancer.
In total, 41 mutations were found in cancerous cells that were not observed in healthy prostate or blood cells. This suggests the mutations are specifically associated with prostate cancer development, says Kloss-Brandstätter.
More mtDNA mutations were found in more advanced cancers, she says, indicating that the mutations could be used to track cancer progression and metastasis.
Mutations drive metabolism
Several mutations were found in genes coding the machinery that makes mitochondrial proteins, and so would probably hinder mitochondria's ability to make the chemical fuel called ATP, which is used by normal cells.
Phillip Nagley of Monash University in Melbourne, Australia, who was not involved in the work, says this could contribute to the changed metabolism typical of cancer cells. Many cancers get energy from glycolysis, which occurs in the liquid inside cells, rather than via aerobic respiration from mitochondria. Ordinary cells use glycolysis for energy only if they are short of oxygen, because it is inefficient.
According to Juergen Reichardt at the University of Sydney, Australia, it's also possible that mtDNA mutations trigger nuclear DNA mutations. Mitochondrial dysfunction could lead to the release of free radicals, which are by-products of aerobic respiration. Free radicals could then lead to nuclear DNA mutations. Reichardt points out, however, that it has not been shown that free radicals released in the mitochondria can enter into the nucleus.
Prostate cancer is currently diagnosed by elevated levels of prostate-specific antigen (PSA). However, the test is far from perfect: PSA levels increase in men with enlarged, but not cancerous prostates. "Additional mtDNA sequencing could lead to a more precise prognosis for the patient," says Kloss-Brandstätter.