Mapping and Cloning Prostate Cancer Predisposition Loci

前列腺癌易感基因的识别已被证明是前列腺癌研究界的一个挑战。虽然已经确定了几个易感基因座，但这些定位都没有导致基因分离，并且只有一个发现得到了显著的验证(Neuhausen等人，1999)。在犹他州，我们最近分离了第一个前列腺癌易感基因(见Tavtigean等人，提交，见附录)，并且已经观察到一些确凿的证据(Rebbeck等人，提交)。在我们10多年的前列腺癌研究中，我们收集了近300个高危前列腺癌家系的资源，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这一努力。我们之前获得了NIH的资助(1994-1998)，以及通过与先灵葆雅的合作伙伴关系获得的资助(1997-2000)；两者都已结束。我们与Myriad Genetics的合作仍在继续。我们正在敲定我们的团队Myriad Genetics、NIH和Johns Hopkins之间的合作协议(后续将发出支持函)，这将导致来自所有团队的数据、结果以及基因组和遗传资源的公开交换，我们希望这将对前列腺癌基因研究做出重大贡献。这项建议支持犹他大学高危家系的收集和分析，以及为实现这一目标而进行的一些无数基因分型工作。

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.