Mapping and Cloning Prostate Cancer Predisposition Loci

前列腺癌易感基因的鉴定已被证明是前列腺研究界的一个挑战。虽然已经确定了几个易感位点，但这些定位都没有导致基因分离，而且这些发现中只有一个得到了显著验证（Neuhausen et al.,1999）。在犹他州，我们最近分离出了第一个前列腺癌易感基因（见Tavtigian等人，在附录中提交），并且已经观察到一些确凿的证据（Rebbeck等人，提交）。在我们超过10年的前列腺癌研究中，我们收集了近300个高风险前列腺癌谱系的资源，存储了大约8000个DNA样本。这些重要的前列腺癌资源和贡献证明了犹他州前列腺癌努力的重要性，我们希望通过这项提案继续下去。我们以前有NIH资助（1994- 1998），并通过与先灵葆雅的合作伙伴关系资助（1997-2000）；两者都结束了。我们与Myriad Genetics的合作仍在继续。我们正在最终确定我们小组、Myriad Genetics、NIH和Johns Hopkins之间的合作协议（将附上支持信），这将导致所有小组的数据、结果、基因组和遗传资源的公开交换，我们希望这将对前列腺遗传研究做出重大贡献。该提案支持犹他大学高风险谱系收集和分析，以及为实现这一目标而进行的一些Myriad基因分型工作。

The identification of prostate cancer predisposition genes has proven to be a challenge for the prostate research community. Although several predisposition loci have been identified, none of these localizations has led to gene isolation, and only one of these findings has been significantly validated (Neuhausen et al.,1999). In Utah we have very recently isolated the first prostate cancer predisposition gene (see Tavtigian et al, submitted, in Appendix), and some confirmatory evidence has already been observed (Rebbeck et al., submitted). During our over 10 years of prostate cancer research we have collected a resource of almost 300 high-risk prostate cancer pedigrees, with approximately 8,000 DNA samples stored. These significant prostate cancer resources and contributions are evidence of the importance of the Utah prostate cancer effort, which we hope to continue through this proposal. We have previously had NIH funding (1994- 1998), and funding through a partnership with Schering Plough (1997-2000); both have ended. Our collaboration with Myriad Genetics continues. We are in the process of finalizing a collaborative agreement between our group, Myriad Genetics, NIH and Johns Hopkins (letters of support will follow), that will result in an open exchange of data, results, and genomic and genetic resources from all groups, and which we hope will contribute significantly to prostate genetic research. This proposal supports the University of Utah high-risk pedigree collection and analysis, and some Myriad genotyping effort towards this goal.