Mitochondrial DNA Mutations and 8-hydroxy-2′-deoxyguanosine Content in Japanese Patients with Urinary Bladder and Renal Cancers

Abstract

Background: Several recent studies have demonstrated the presence of mitochondrial DNA (mtDNA) mutations in various human cancers. The origin of these mutations may be attributable to oxidative damage from reactive oxygen species (ROS). In order to investigate the relationship between mtDNA mutations and ROS in human cancers, urinary bladder and renal cancers were examined for mutations in the displacement-loop (D-loop) region of mtDNA and for 8-hydroxy-2′-deoxyguanosine (8-OHdG) content. Materials and Methods: The D-loop region of mtDNA of Japanese patients with urinary bladder or renal cancers was examined by direct sequencing. The level of 8-OHdG was measured in the patients who had undergone radical cystectomy or nephrectomy from excised specimens. Results: Somatic mutations in the D-loop region were detected in 7 (23%) out of 31 patients with bladder cancer and 3 (14%) out of 21 patients with renal cancer. The most frequent mutations were in the poly(C) mononucleotide repeat located at positions 303 to 309. The levels of 8-OHdG in cancer tissues were significantly higher than in the neighboring non-cancerous tissues, but many of the cancers with an elevated 8-OHdG level did not display D-loop mutations. Conclusion: These results suggest that the D-loop region of mtDNA might have a genetic instability in cancer tissues independently from the 8-OHdG level.