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Junjian Z Chen

Publications and source records attributed to Junjian Z Chen.

5 recordsLinked to original sources
PubMed2004

Mitochondrial mutagenesis and oxidative stress in human prostate cancer.

Prostate cancer is the most common cancer diagnosed in men in the United States, but the primary cause and the molecular events leading to prostate carcinogenesis are poorly understood. Using the approach of laser capture microdissection, we revealed extensive somatic mitochondrial DNA (mtDNA) mutations in prostatic neoplastic lesions. Inspection of the lesion associated mutations not only provided new insights into the genetics of prostate cancer, but also revealed new patterns of mtDNA mutation in prostate carcinogenesis. Further analysis on a high frequency of multiple mutational events observed in the same neoplastic lesion revealed an unusually rapid process in mitochondrial mutagenesis, suggesting a new process of mitochondrial hyper-mutagenesis in cancer cells, likely mediated by cellular oxidative stress. Thus, active mitochondrial mutagenesis in prostate cancer suggests a prominent role of increased cellular oxidative stress in neoplastic transformation and the increased susceptibility of neoplastic cells to oxidative damage.

DNA, Mitochondrial↗
PubMed2003

Simultaneous generation of multiple mitochondrial DNA mutations in human prostate tumors suggests mitochondrial hyper-mutagenesis.

Multiple somatic mitochondrial DNA mutations are frequently reported in human tumors, but the process 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 mitochondrial (mt)DNA 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 co-exists 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, probably mediated by cellular oxidative stress, to account for a burst of multiple mtDNA mutations in human prostate tumors.

Base Sequence↗
PubMed2003

Genetic differentiation at nuclear and mitochondrial loci among large white-headed gulls: sex-biased interspecific gene flow?

We measured genetic differentiation among species of large white-headed gulls using mitochondrial (cytochrome b haplotypes) and nuclear (microsatellites) markers. Additional information was added using a previously published study of allozymes on the same species. Levels of differentiation among species at nuclear markers are much lower than would be expected for avian species and are not concordant with the level of differentiation in mitochondrial markers. This discrepancy is best explained by a combination of recent species origin and interspecific gene flow after speciation. The data also suggest that female-mediated gene flow is reduced compared to male-mediated gene flow, either due to behavioral bias or due to stronger counterselection of female hybrids in accordance with Haldane's rule for ZW species. Whatever the reasons for the low differentiation of the species' nuclear gene pools, the extensive similarity of their nuclear genome demonstrates that selection on a limited number of characters is an important factor in establishing and maintaining clear-cut phenotypic differences between these species and suggests that the number of loci involved in this process is quite low. This situation may not be exceptional in birds, indeed a number of studies have found similarly low level of differentiation in nuclear markers among congeneric bird species, although usually based on a single set of markers. Because hybridization is a widespread phenomenon in birds, many of these cases might be due to interspecific gene flow.

Animals↗
PubMed2002

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.

Aged↗