A new study that found DNA mutations throughout the mitochondrial genome were linked to increased levels of prostate specific antigen (PSA) and prostate cancer itself raises the interesting suggestion that perhaps screening a man’s mitochondrial genome could increase the accuracy of the PSA test.
In a study that appeared online in the journal American Journal of Human Genetics on 2 December, Austrian researchers described how they compared mitochondrial DNA from cancerous tissue with that of benign tissue for each of 30 Austrian men with various stages of prostate cancer, and found 41 mutations in cancerous cells that they could not find in healthy prostate or blood cells.
Mitochondria are tiny “batteries” inside each cell that make the energy used by the cell. They have their own DNA which is separate from the DNA of the cell nucleus.
Research published last year showed that mitochondrial DNA (mtDNA) mutations were linked to prostate cancer, but senior author Dr Anita Kloss-Brandstätter, of Innsbruck Medical University, and colleagues, wanted to take this further and look across the whole mitochondrial genome, comprising over 16,500 base pairs.
Kloss-Brandstätter told the press this was the first study to target the “entire mitochondrial genome in prostate cancer and benign tissue from the same patient with a superior sequencing strategy”.
She and her colleagues found that the men with the more advanced cancers had more more mutations, suggesting these could be used as markers of cancer progression and spread.
They wrote that “sequencing of selected mitochondrial regions will likely result in a mutation spectrum useful for prognosis”.
“These findings will potentially help others monitor malignant transformation, tumor progression, and metastasis,” said Kloss-Brandstätter.
But perhaps the most striking result was when they detected a strong link between “somatic tRNA” mutations and PSA levels at diagnosis.
“Patients with a somatic tRNA mutation had a significantly higher PSA value at diagnosis than did patients without a somatic tRNA mutation”, said Kloss-Brandstätter.
tRNA has a particular role in mitochondrial protein synthesis: it flies around like a little helicopter and drops amino acid molecules into the right places to make the proteins.
Mutations in tRNA would probably interfere with the mitochondria’s ability to make ATP, that normal cells use as a source of energy.
Mitochondria make ATP via aerobic respiration, but as Phillip Nagley of Monash University in Melbourne, Australia, remarked to New Scientist recently, many cancer cells get their energy from glycolysis, which occurs in the liquid inside cells rather than the aerobic respiration process of the mitochondria.
Aerobic respiration is more efficient for energy production, and normal cells only use glycolysis if they are short of oxygen. But cancer cells may also get a boost from the fact glycolysis also produces the chemical building blocks for making cells, which they need to grow and multiply.
This could be a factor in the changed metabolism typical of cancer cells, said Nagley.
Prostate cancer is one of the most common cancers diagnosed in the US and Europe, and the most common way to test for it non-invasively is the PSA blood test, which is routinely done in some countries for men aged 50 and over.
However, while generally speaking the higher the level of PSA, the more likely it is that the patient has prostate cancer, PSA can also be raised for other reasons, such as due to an enlarged but benign prostate or an infection. The result would still have to be confirmed with a biopsy of the prostate, which is invasive, and not without risk.
Adding mitochondrial DNA sequencing to the PSA test could lead to a more precise diagnosis for patients, said Kloss-Brandstätter.
“Somatic Mutations throughout the Entire Mitochondrial Genome Are Associated with Elevated PSA Levels in Prostate Cancer Patients.”
Anita Kloss-Brandstätter, Georg Schäfer, Gertraud Erhart, Alexander Hüttenhofer, Stefan Coassin, Christof Seifarth, Monika Summerer, Jasmin Bektic, Helmut Klocker, Florian Kronenberg.
DOI:10.1016/j.ajhg.2010.11.001
Additional Sources: New Scientist (“Is mitochondrial DNA the secret of prostate cancer?” 20 December 2010), Cell Press (press release, 2 December 2010).
Written by: Catharine Paddock, PhD