Researchers find DNA mutations key to prostate cancer
Mutations in mitochondrial DNA (mtDNA) are key to the development of prostate cancer, according to research by scientists at Emory University School of Medicine and the University of California, Irvine. Mitochondrial DNA, which is separate from nuclear DNA, is found in the hundreds of mitochondria located in the cytoplasm outside of each cell's nucleus. The mitochondria are often called the "powerhouse" of the cell because they produce about 90% of the body's energy. The researchers sequenced segments of mtDNA from prostate cancer patients and found a variety of mutations, including various mutations in the mtDNA cytochrome oxidase subunit (COI) gene. They then sequenced the COI gene in 260 prostate cancer tissue samples or blood cells from patients with confirmed cancer who had undergone radical prostatectomies, and 54 tissue samples from patients who had prostate biopsies but were found to be cancer free. They found that 12% of all the prostate cancer samples had mutations in the COI gene, while less than 2% of the samples from patients found to be cancer free harbored mutations in this gene. In a control sample of 1,019 individuals from the general population, 7.8% had mutations in the COI gene. The researchers found both germ-line (inherited) and somatic (acquired) mutations in the prostate cancer samples. To determine whether mtDNA mutations are causally related to prostate cancer, the researchers introduced into a prostate cancer cell line mtDNAs harboring a known disease-causing mtDNA mutation. The prostate cancer cells with the mutant mtDNAs generated tumors that were on average seven times larger than the prostate cancer cells with normal mitochondria. Hence, the deleterious mtDNA mutation greatly enhanced prostate cancer growth. "We believe this study provides convincing evidence that mitochondrial mutations play an important role in prostate cancer," said Dr John Petros, associate professor of urology and pathology at Emory University School of Medicine and the Winship Cancer Institute. "This is the first evidence that individuals who inherit a mutation of the mitochondrial DNA are at an increased risk of developing prostate cancer later in life. Interestingly, mitochondrial DNA is inherited from your mother, so this may explain those familial cases that are not passed from father to son, but rather through the unaffected mother to her sons."