Carcinogenesis Advance Access published online on July 17, 2003
Carcinogenesis, doi:10.1093/carcin/bgg102
© 2003 by Oxford University Press
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CANCER BIOLOGY
1 Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR 72079, USA
* Corresponding author. E-mail: jjchen{at}nctr.fda.gov.
Received 11 April 2003
; revised 2 June 2003
; accepted 14 June 2003
Multiple somatic mitochondrial DNA mutations are frequently reported in human tumors, but the process that leading to homoplasmic transformation and accumulation of multiple mutations in the same tumor cell lineage remains a mystery. We address possible mechanisms responsible for the generation of multiple mtDNA mutations observed in a high frequency of prostate tumors using sensitive mutant-specific PCR coupled with laser capture microdissection. Analysis of prostate tumors with multiple mtDNA mutations in the control region indicates that the mutations are locally confined, that the multiple mutations exist on the same molecules and that more than one mtDNA mutant species coexists in the same neoplastic lesion. These results suggest an unusually rapid process in mtDNA mutagenesis during tumor progression. On the basis of prostate tumor cell kinetics, we propose a unique process of mitochondrial hyper-mutagenesis, likely mediated by cellular oxidative stress, to account for a burst of multiple mtDNA mutations in human prostate tumors.
Mitochondrial DNA, mutagenesis, prostate cancer, allele-specific PCR, laser capture microdissection
Simultaneous generation of multiple mitochondrial DNA mutations in human prostate tumors suggests mitochondrial hyper-mutagenesis
2 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
3 Department of Urology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
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