EXPRESSION MONITORING OF MULTIPLEXED CANCER GENE SETS

分子遗传学需要新的方法来深入了解致癌的许多可能机制和治疗药物的作用。这种需求延伸到药理学和肿瘤学领域的快速筛选方法，其中在基因表达和调控方面对癌症进展和预防的评估和后果具有重大意义。我们已经开发了一种新的方法，定量，多重基因表达分析的基础上，新的标记方法和质谱。这项技术作为一种方法，将使癌症研究人员能够以比目前可能的低得多的成本获得关于基因突变和环境影响的遗传效应的大量信息。在第一阶段，它提出了验证这种技术用于癌症相关基因的基因表达的研究。建议的商业应用：高通量基因表达监测在药物开发中具有广泛的商业应用。作为该提案的一部分，正在开发的方法可用于初级和二级化学筛选，以确定新的化学预防和化学治疗剂。进一步的效用包括筛选化学毒性和使用多变量析因实验破译复杂表达反应的能力。

There is a need for new methods in molecular genetics to provide insight into the many possible mechanisms of carcinogenesis and effects of therapeutic agents. This need extends to rapid screening methodologies in the field of pharmacology and oncology, where the evaluation and consequences of cancer progression and prevention in terms of gene expression and regulation is of major interest. We have developed a new methodology for quantitative, mulitplexed gene expression analysis based on novel labeling methods and mass spectrometry. This technology has much promise as an approach that will enable cancer researchers to acquire large volumes of information on the genetic effects of genetic mutations and environmental influences at a much lower cost than is currently possible. In Phase I, it is proposed to validate this technology for use in the study of gene expression of cancer-related genes. PROPOSED COMMERCIAL APPLICATIONS: High throughput gene expression monitoring has broad commercial application within pharmaceutical development. The methods being developed as part of this proposal may be used for primary and second chemical screens to identify new chemopreventive and chemotherapeutic agents. Further utility includes screens for chemical toxicity and the ability to decipher complex expression responses using multivariable factorial experiments.