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。 虽然已经鉴定了几个易感基因座，但是这些定位都没有导致基因分离，并且这些发现中只有一个得到了显著验证（诺伊豪森et al.，1999年）。 在犹他州，我们最近已经分离出第一个前列腺癌易感基因（参见Tavtigian等人，在附录中提交），并且已经观察到一些确证性证据（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个高危前列腺癌谱系的资源，储存了大约8，000个DNA样本。这些重要的前列腺癌资源和贡献是犹他州前列腺癌工作重要性的证据，我们希望通过这一提议继续下去。 我们以前曾获得NIH资助（1994- 1998），并通过与先灵葆雅的合作伙伴关系获得资助（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和约翰霍普金斯之间的合作协议（支持信将随后），这将导致来自所有团体的数据，结果和基因组和遗传资源的开放交流，我们希望这将对前列腺遗传研究做出重大贡献。 这项提议支持犹他州大学的高风险家系收集和分析，以及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.