Extensive somatic mitochondrial mutations in primary prostate cancer using laser capture microdissection.
Prostate cancer is the second leading cause of cancer deaths among men in the United States,but the precise molecular events leading to prostate carcinogenesis are not well understood. We isolated histologically defined cell populations from prostate cancer and its preinvasive lesions using laser capture microdissection, and performed genetic analysis on the mitochondrial genome, a sensitive cytoplasmic DNA. An extremely high incidence of somatic mutation (90% of prostatectomy cancer specimens) was found in the control region (the displacement loop) of mitochondrial DNA. The massive induction of lesion-associated mutations suggests active mitochondrial mutagenesis in both prostate cancer and its preinvasive lesions. Inspection of these mutations provides new insights into prostate cancer genetics and reveals unique patterns of somatic mutations in prostatic neoplastic lesions.
Chen
Junjian Z
JZ
Division of Molecular Epidemiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, USA. jjchen@nctr.fda.gov
Gokden
Neriman
N
Greene
Graham F
GF
Mukunyadzi
Perkins
P
Kadlubar
Fred F
FF
D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D007834:Lasers; D008297:Male; D008846:Micromanipulation / Q000379:methods*; D008875:Middle Aged; D005810:Multigene Family; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm