LARGE SCALE GENE DISCOVERY--HUMAN PROSTATE CANCER

描述：(改编自调查人员的摘要)EST(表示 Sequence Tag)范例以随机对表达的短延伸片段进行排序 作为识别全长cDNA的手段的基因区域受到了挑战 由于缺乏技术创新来弥补这项技术的不足 脱下来。这个行业现在有数以百万计的EST，但无法扩展 这一发现过程到鉴定和表征 全长基因。Origene Technologies，Inc.(OTI)已经开发出两种 允许高通量全长cDNA的互补技术 克隆。在这个快速通道第一阶段-第二阶段的应用中，OTI提出了一个基因 以人类前列腺癌为目标的发现计划。在阶段I组件中， 申请者建议生成高质量的原始材料，这将 在二期阶段支持大规模、全长的cDNA分离。三 提出了以下具体目标：(1)构建正常前列腺组织的cDNA文库 组织和前列腺癌，(2)排列每个组织和前列腺癌的cDNA克隆 库到一级和二级多层板上，以及(3)执行 对这些图书馆进行了严格的质量控制。 前列腺癌是世界上最常见的人类癌症。 美国。申请者声称，许多在前列腺中起作用的基因 癌变可以作为有用的诊断工具和/或作为 治疗性干预。在第二阶段组成部分中，开发了原始材料 在第一阶段，将使用组分来分离200个全长cDNA 克隆，根据其前列腺特异性或前列腺癌进行选择 癌症特有的表达模式。申请者提出：(1)发展 筛选可能在前列腺中发挥作用的重要EST的方法 生长与致癌，(2)分离相应的全长cDNAs (3)5‘端DNA的测定 每个人的序列，并确认其真实性。这个发现过程是 可能会超出本申请中提议的工作范围。 建议的商业应用：不可用

DESCRIPTION: (Adapted from the investigator's abstract) The EST (expressed sequence tag) paradigm to randomly sequence short stretches of expressed regions of genes as a means to identify full-length cDNAs, has been challenged by the lack of technological innovations to pick up where this technology left off. The industry is now guttered with millions of ESTs but is unable to extend this discovery process to the identification and characterization of full-length genes. OriGene Technologies, Inc. (OTI) has developed two complementary technologies which allow high-throughput full-length cDNA cloning. In this fast-track Phase I - Phase II application, OTI proposes a gene discovery program that targets human prostate cancer. In the Phase I component, the applicants propose to generate high-quality source material which will support large-scale, full-length cDNA isolation at the Phase II stage. Three specific aims are proposed: (1) generating cDNA libraries from normal prostate tissue and prostatic adenocarcinomas, (2) arraying the cDNA clones from each library onto primary and secondary multi-level plates, and (3) performing stringent quality controls on these library. Prostate carcinoma is the most frequently diagnosed form of human cancer in the United States. The applicants assert that many genes which function in prostate carcinogenesis could serve as useful diagnostic tools and/or as targets for therapeutic intervention. In the Phase II component, source materials developed in the Phase I component will be used to isolate two hundred full-length cDNA clones, selected on the basis of their prostate-specific or prostate cancer-specific expression patterns. The applicants propose: (1) developing approaches to select important ESTs that potentially play a role in prostate growth and carcinogenesis, (2) isolating their corresponding full-length cDNA clones from the arrayed cDNA library panels, and (3) determining the 5' DNA sequence of each and confirming its authenticity. This discovery process is likely to extend beyond the work proposed in this application. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE