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Science 17 March 2000:
Vol. 287. no. 5460, pp. 2017 - 2019
DOI: 10.1126/science.287.5460.2017
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Reports

Facile Detection of Mitochondrial DNA Mutations in Tumors and Bodily Fluids

Makiko S. Fliss, 1 Henning Usadel, 1 Otávia L. Caballero, 1 Li Wu, 1 Martin R. Buta, 1 Scott M. Eleff, 2 Jin Jen, 1 David Sidransky 1*

Examination of human bladder, head and neck, and lung primary tumors revealed a high frequency of mitochondrial DNA (mtDNA) mutations. The majority of these somatic mutations were homoplasmic in nature, indicating that the mutant mtDNA became dominant in tumor cells. The mutated mtDNA was readily detectable in paired bodily fluids from each type of cancer and was 19 to 220 times as abundant as mutated nuclear p53 DNA. By virtue of their clonal nature and high copy number, mitochondrial mutations may provide a powerful molecular marker for noninvasive detection of cancer.

1 Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division,
2 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed. E-mail: dsidrans{at}jhmi.edu

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The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method.
D. G. Murdock, N. C. Christacos, and D. C. Wallace (2000)
Nucleic Acids Res. 28, 4350-4355
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Predicting Lung Cancer by Detecting Aberrant Promoter Methylation in Sputum.
W. A. Palmisano, K. K. Divine, G. Saccomanno, F. D. Gilliland, S. B. Baylin, J. G. Herman, and S. A. Belinsky (2000)
Cancer Res. 60, 5954-5958
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Aberrant Methylation of Gene Promoters in Cancer--Concepts, Misconcepts, and Promise.
S. B. Baylin, S. A. Belinsky, and J. G. Herman (2000)
J Natl Cancer Inst 92, 1460-1461
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Canaries in the Coal Mine : Mitochondrial DNA and Vascular Injury From Reactive Oxygen Species.
R. S. Williams (2000)
Circ. Res. 86, 915-916
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Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues.
E. Nekhaeva, N. D. Bodyak, Y. Kraytsberg, S. B. McGrath, N. J. Van Orsouw, A. Pluzhnikov, J. Y. Wei, J. Vijg, and K. Khrapko (2002)
PNAS 99, 5521-5526
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The Complete Sequence of the Zebrafish (Danio rerio) Mitochondrial Genome and Evolutionary Patterns in Vertebrate Mitochondrial DNA.
R. E. Broughton, J. E. Milam, and B. A. Roe (2001)
Genome Res. 11, 1958-1967
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