Quantitative analysis of mitochondrial DNA 4977-bp deletion in sporadic breast cancer and benign breast diseases
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The mitochondrial DNA (mtDNA) 4977-bp deletion (ΔmtDNA4977 mutation) is one of the most frequently observed mtDNA mutations in human tissues and may play a role in carcinogenesis. Only a few studies have evaluated ΔmtDNA4977 mutation in breast cancer tissue, and the findings have been inconsistent, which may be due to methodological differences. In this study, we developed a quantitative real-time PCR assay to assess the level of the ΔmtDNA4977 mutation in tumor tissue samples from 55 primary breast cancer patients and 21 patients with benign breast disease (BBD). The ΔmtDNA4977 mutation was detected in all of the samples with levels varying from 0.000149% to 7.0%. The ΔmtDNA4977 mutation levels were lower in tumor tissues than in adjacent normal tissues in both breast cancer and BBD subjects. The differences, however, were not statistically significant. No significant difference between breast cancer and BBD patients was found in the ΔmtDNA4977 mutation levels of tumor tissues and adjacent normal tissues. The ΔmtDNA4977 mutation levels were not significantly associated with clinicopathological characteristics (age, histology, tumor stage, and ER/PR status) in breast cancer or BBD patients. These results do not support the notion that the mitochondrial DNA 4977-bp deletion plays a major role in breast carcinogenesis.
KeywordsBenign breast disease Breast cancer mtDNA 4977-bp deletion Quantitative real-time PCR assay
We thank Dr. Konrad Huppi (Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD) for kindly providing mitochondrial DNA samples, Bethanie Hull and Brandy Venuti for technical assistance in the preparation of this article, and all of the study participants and research staff of the Shanghai Breast Cancer Study for their support. This research was supported by U.S. Department of Defense grant DAMD17-02-1-0603 and National Cancer Institute grant R01 CA064277.
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