This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have previously shown that genomic copy number analysis of multiple metastases from men with metastatic prostate cancer can be used to distinguish clonal from nonclonal genomic changes. Recent carbon-14 based studies have proven valuable in establishing the rate of cell turnover in myocardium and other tissues. The primary aim of a carbon-14 based study of metastatic prostate cancer DNA is to establish the relative age of various metastases in a given individual with metastatic prostate cancer, to provide valuable new insight into the natural history of metastatic cancer lesions. The scientific purpose is to understand the natural history of metastatic cancer, so that diagnostic methods and treatment can be better tailored to each person with metastatic cancer. Do all metastases in an individual have a similar profile, or are they measurably different in age, and do these differences in age correspond to differences in clonal and subclonal copy number changes? Genomic DNA samples for the study are from the Johns Hopkins Integrated Clinical ?Genomic Autopsy Study of Lethal Prostate Cancer. DNA samples studied include at least three anatomically separate metastatic sites and at least one noncancerous DNA sample from up to 12 subjects. The AMS technique is the only method with sufficient accuracy and precision to measure bomb-pulse carbon-14 in relatively small DNA samples.
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