CARBON-14 BASED AGE ANALYSIS OF METASTATIC PROSTATE CANCER SAMPLES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们先前已经证明，转移性前列腺癌患者多处转移的基因组拷贝数分析可以用来区分克隆性和非克隆性基因组变化。最近基于碳14的研究已被证明在确定心肌和其他组织中的细胞周转率方面有价值。基于碳14的转移性前列腺癌DNA研究的主要目的是确定转移性前列腺癌患者的各种转移的相对年龄，为了解转移性癌症病变的自然历史提供有价值的新见解。 科学目的是了解转移性癌症的自然历史，以便更好地为每个转移性癌症患者量身定做诊断方法和治疗方法。一个人的所有转移瘤是否都有相似的特征，或者它们在年龄上有明显的不同，这些年龄上的差异是否与克隆和亚克隆拷贝数变化的差异相对应？这项研究的基因组DNA样本来自约翰·霍普金斯大学致命前列腺癌的综合临床基因组尸检研究。所研究的DNA样本包括至少三个解剖上分离的转移部位和至少一个来自多达12名受试者的非癌症DNA样本。AMS技术是在相对较小的DNA样本中测量炸弹脉冲碳-14的唯一具有足够准确度和精密度的方法。

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.