Mitochondrial DNA mutations in prostate cancer bone metastases

Prostate cancer is the most common non-skin cancer in men. Those with local or regional disease often have good long-term prognosis, but patients with metastatic disease face high morbidity and mortality. The vast majority of cases with distant spread have some degree of bony involvement. The reason for the disproportionately high percentage of metastasis to bone relative to other metastatic sites remains unclear. A growing body of evidence suggests mitochondrial DNA (mtDNA) is associated with prostate cancer, and the effects of mtDNA on tumor growth may be augmented by the bone microenvironment. Here, we review our latest study analyzing mtDNA mutations in 10 patients with advanced prostate cancer and both bone and soft tissue metastases. This cohort of patients had significantly increased somatic mtDNA mutations in bone metastasis compared to paired primary tumor and soft tissue metastasis. In addition, a recurrent mtDNA mutation at nucleotide position 10398, was exclusively found in bone metastasis in 7 of 10 patients with advanced prostate cancer, with no such mutations found in paired benign prostate, primary tumor, or soft tissue metastasis. We describe the results from this work and review the relevant literature on the role of mitochondrial DNA in prostate cancer bone metastases.