This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Traditional methods used for dating cells are limited in the information they provide, or are not appropriate for human use. We developed a method for the retrospective birth dating of cells using bomb pulse carbon-14 (14C) dating as a method for measuring the approximate age of specific populations of cells in the adult human brain and other tissues. This method is based on establishing the proportion of the isotope 14C in genomic DNA. After a cell has terminally differentiated it does not divide again. Since the last cell division represents the last time point when the cell synthesized DNA, its chromosomal DNA will reflect the age when the cell was born. Traditionally, the slow decay of 14C relative to other carbon isotopes has given it a temporal resolution of many years, however due to nuclear tests in the late 1950s and early 1960s, the level of 14C in the atmosphere doubled. This level has since dropped off in an exponential fashion, allowing one to resolve 14C differences in the range of years. Because DNA has a 14C content reflective of the time when it was synthesized, establishing the 14C content of chromosomal DNA will enable us to retrospectively birth date cells, and thus establish cellular turnover. Dr. G Steven Bova from Johns Hopkins School of Medicine wants to apply the DNA dating technique to archived primary and metastatic prostate tumors to gain information on the natural progression of metastatic cancer lesions. Dr. Bova's team recently published an extensive study showing that genetic copy number analysis of multiple metastases from men with metastatic prostate cancer can distinguish clonal from non-clonal genomic changes.
The aim of the of the study is to establish the relative age of various metastases in an individual with prostate cancer, to provide valuable insight into the natural history of metastatic cancer lesions.
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