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JMD 2006, Vol. 8, No. 3
Copyright © 2006 American Society for Investigative Pathology & Association for Molecular Pathology

Somatic Mitochondrial DNA Mutations in Prostate Cancer and Normal Appearing Adjacent Glands in Comparison to Age-Matched Prostate Samples without Malignant Histology

Ryan L. Parr*, Gabriel D. Dakubo*, Keith A. Crandall§, Jennifer Maki*, Brian Reguly*, Andrea Aguirre*, Roy Wittock*, Kerry Robinson*, Jude S. Alexander*, Mark A. Birch-Machin{dagger}, Mamdouh Abdel-Malak{ddagger}, M. Kent Froberg, Eleftherios P. Diamandis|| and Robert E. Thayer*

From Genesis Genomics Incorporated, * Thunder Bay, Ontario, Canada; the Thunder Bay Regional Health Sciences Centre, {ddagger} Thunder Bay, Ontario, Canada; Dermatological Sciences, {dagger} University of Newcastle, Newcastle upon Tyne, United Kingdom; the Department of Integrative Biology, § Brigham Young University, Provo, Utah; Pathology and Laboratory Medicine, University of Minnesota, Duluth, Minnesota; and the Department of Laboratory Medicine and Pathology, || University of Toronto, Toronto, Ontario, Canada

Studies of somatic mitochondrial DNA mutations have become an important aspect of cancer research because these mutations might have functional significance and/or serve as a biosensor for tumor detection. Here we report somatic mitochondrial DNA mutations from three specific tissue types (tumor, adjacent benign, and distant benign) recovered from 24 prostatectomy samples. Needle biopsy tissue from 12 individuals referred for prostate biopsy, yet histologically benign (symptomatic benign), were used as among individual control samples. We also sampled blood (germplasm tissue) from each patient to serve as within individual controls relative to the somatic tissues sampled (malignant, adjacent, and distant benign). Complete mitochondrial genome sequencing was attempted on each sample. In contrast to both control groups [within patient (blood) and among patient (symptomatic benign)], all of the tissue types recovered from the malignant group harbored significantly different mitochondrial DNA (mtDNA) mutations. We conclude that mitochondrial genome mutations are an early indicator of malignant transformation in prostate tissue. These muta-tions occur well before changes in tissue histo-pathology, indicative of prostate cancer, are evident to the pathologist.




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J. Chen, F. F. Kadlubar, and J. Z. Chen
DNA supercoiling suppresses real-time PCR: a new approach to the quantification of mitochondrial DNA damage and repair
Nucleic Acids Res., March 13, 2007; (2007) gkm010v2.
[Abstract] [Full Text] [PDF]


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