Abstract

We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4mt ) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4mt was identified through long-extension polymerase chain reaction (PCR) analysis of frozen prostate cancer samples. A quantitative PCR assay was developed to measure the levels of the 3.4mt in clinical samples. For normalization, amplifications of a nuclear target and total mitochondrial DNA were included. Cycle threshold data from these targets were used to calculate a score for each biopsy sample. In a pilot study of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between benign and malignant core biopsy specimens was well differentiated (P < .0001), with PTM indistinguishable from malignant samples (P = .833). Results of a larger study were identical. In comparison with histopathologic examination for benign and malignant samples, the sensitivity and specificity were 80% and 71%, respectively, and the area under a receiver operating characteristic (ROC) curve was 0.83 for the deletion. In a blinded external validation study, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.87. The 3.4mt may be useful in defining malignant, benign, and PTM prostate tissues.

Author notes

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These authors work for and own stock options in Genesis Genomics.
Financial support for this project was provided to Genesis Genomics by Industry Canada (FedNor), Sudbury, Canada, and Northern Ontario Heritage Fund Corporation (NOHFC), Sault Ste Marie, Canada. Funding was also provided for this study by an interagency agreement (Y1CN5001-01) between the National Institute of Standards and Technology and the National Cancer Institute.
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