{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:07:55Z","timestamp":1764781675205},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,5,17]],"date-time":"2006-05-17T00:00:00Z","timestamp":1147824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Somatic mutations at a mitochondrial noncoding polycytidine (C)<jats:sub>n<\/jats:sub> repeat (polyC) have been associated with tumor progression. We analyzed whether these alterations are due to the inherent mutability of repeated sequences. Insertion and deletion mutations were found in colon (<jats:italic>n<\/jats:italic> = 114), stomach (<jats:italic>n<\/jats:italic> = 105), endometrium (<jats:italic>n<\/jats:italic> = 53), breast (<jats:italic>n<\/jats:italic> = 45), lung (<jats:italic>n<\/jats:italic> = 35), and prostate (<jats:italic>n<\/jats:italic> = 20) tumors. The mutation frequency in colon, gastric, and endometrial tumors was 23, 17, and 11%, respectively, which paralleled the relative extent of microsatellite instability in long mononucleotide repeats observed in tumors with mismatch repair deficiency (colon &gt; stomach &gt; endometrium, relative ratio 10:8:4). Colon tumors with mutations of more than one nucleotide were more advanced in tumor progression. Further, two tumors showing a T &gt; C mutation that restored the homopolymeric repeat, harbored sequential deletion mutations of up to 4 and 6 nucleotides. These results illustrate that the increased mutability of repeated mitochondrial sequences is dependent on the repetitive structure of the DNA molecule and suggest that mutations in the (C)<jats:sub>n<\/jats:sub> repeat, whether homoplasmic or not, and by extrapolation, mitochondrial mutations in general, are not the result of selective pressure during tumorigenesis. We also suggest that the (C)<jats:sub>n<\/jats:sub> repeat may be used as an universal molecular clock to estimate the relative mitotic history of tumors. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20340","type":"journal-article","created":{"date-parts":[[2006,5,17]],"date-time":"2006-05-17T16:31:02Z","timestamp":1147883462000},"page":"770-780","source":"Crossref","is-referenced-by-count":21,"title":["Mutational dynamics in human tumors confirm the neutral intrinsic instability of the mitochondrial D\u2010loop poly\u2010cytidine 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