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Somatic mutations of mitochondrial genome in early stage breast cancer

The complete mitochondrial genomes of the primary cancerous, matched paracancerous normal and distant normal tissues from 10 early‐stage breast cancer patients were analyzed in this study, with special attempt (i) to investigate whether the reported high frequency of mitochondrial DNA (mtDNA) somatic mutations in breast cancer could be repeated under a stringent data quality control, and (ii) to characterize the spectrum of mtDNA somatic mutations in Chinese breast cancer patients and evaluate their potential significance in early cancer diagnosis. Two heteroplasmic somatic transitions (T2275C and A8601G) were identified in our samples. The transition A8601G was present in the primary cancerous and paracancerous normal tissues from patient no. 3. Transition T2275C was found in the primary cancerous tissue but not in other normal tissues from patient no. 6; this transition has been reported in the colonic crypts and is located at a highly conserved site in the 16S rRNA gene. Subsequent cloning sequencing confirmed the absence of both mutations in the distant normal tissues from the 2 patients. The overall rate of somatic mutations in our patients was much lower than those of previous studies of breast cancer. Our results gave support to the recent claim that the high frequency of mtDNA somatic mutations in cancer studies is overestimated. Based on the mtDNA mutation pattern in early stage breast cancer observed in this study, we cautioned the enthusiasms and efforts to look for somatic mutations that were of diagnostic value in cancer early detection. © 2007 Wiley‐Liss, Inc.