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        Identification of mtDNA Mutations in Human Cancer

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        The human mitochondrial genome is composed of a 16-kb circular, doublestranded DNA that encodes 13 polypeptides of the mitochondrial respiratory chain, 22 transfer RNAs, and 2 ribosomal RNAs required for protein synthesis (1 ). It is generally accepted that mitochondrial DNA (mtDNA) mutations are generated during oxidative phosphorylation through pathways involving reactive oxygen species (ROS) (2 ). In a recent breakthrough, several mtDNA mutations were found specifically in human colorectal cancer (3 ). We and others also detected frequent mutations in bladder, head and neck, lung tumors, pancreas, and hepatocellular carcinoma (4 6 ). These mutations were scattered throughout the coding and noncoding regions of the mtDNA in the various tumors studied. Many, but not all, coding mutations were confined to respiratory complex I (3 ,7 ). Of particular interest, the noncoding displacement-loop (D-loop) region was found to be a mutational hot spot in our studies (4 ).
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