Abstract
The role, if any, that mitochondrial (mt) DNA alterations play in the carcinogenic process remains unclear. To determine whether mtDNA instability occurs in cancers, nine microsatellite sequences in the mtDNA were examined in 45 sporadic colorectal carcinomas. Alteration in a polycytidine (C)n tract within a non-coding displacement-loop (D-loop) region was detected in 20 carcinomas (44%), three of which also exhibited frameshift mutations in a polyadenosine (A)8 or polycytidine (C)6 tract within NADH dehydrogenase (ND) genes. Interestingly, all three mutant genes were predicted to encode truncated ND proteins, which lacked a large portion of the C-terminus. These results suggested that certain repair systems, like the mismatch repair systems in the nuclear genome, are required for mtDNA maintenance and that defects in these systems can lead to target mitochondrial gene mutations in colorectal carcinomas.
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