Cancer Vertical Arrays

描述(由申请人提供)： 肿瘤分子生物学的实验挑战之一是评估生物标记物的有效性和通用性。这已经成为从微阵列研究揭示的差异基因表达开发生物标记物的关键瓶颈。在这项建议中，我们发展了使用垂直阵列来探索癌症差异基因表达的概念。垂直阵列同时探索一个基因在许多生物样本中的表达，而标准微阵列一次探索许多基因对一个生物变量的响应。在这方面，垂直阵列就像点斑点，但垂直阵列印刷在玻璃片上，使它们具有更好的信噪比行为，并且，不是在每个点中发现RNA群体的整个复杂性，而是将RNA群体划分为多个点。这些低复杂度的表示具有卓越的信噪比性能。这项建议中的工作将集中于建立垂直阵列的可行性，以同时研究多个癌症样本中的基因调控。潜在的吞吐量非常高，因此可以同时研究每个肿瘤的多个区域。这种方法将有助于确认某个基因确实受到差异调控，确定该基因在转化的正常组织和周围正常组织中的表达分布，以及确定该基因在同一类型癌症的不同情况下和不同类型的癌症中是否表现出相似的方式。这些目标需要广泛而有效的显微解剖，我们已经建造了一种新的仪器--“组织研磨机”--来实现这些目的。相关性：生物标志物对诊断、预后和作为癌症的潜在治疗靶点是有用的。有数百种潜在的生物标志物，但在它们可以被开发之前，还需要进一步的验证。

DESCRIPTION (provided by applicant): One of the experimental challenges in cancer molecular biology is assessing the validity and generality of biomarkers. This has become a critical bottleneck in the development of biomarkers from differential gene expression revealed by microarray studies. In this proposal, we develop the concept of using vertical arrays for exploration of differential gene expression in cancer. Vertical arrays explore the expression of a gene in many biological samples simultaneously, whereas standard microarrays explore the expression of many genes in response to one biological variable at a time. Vertical arrays are like dot blots in this regard, but vertical arrays are printed on glass slides, giving them better signal-to-noise behavior, and, rather than spotting the entire complexity of the RNA population in each spot, the RNA population is divided up among multiple spots. These low complexity representations have superb signal-to-noise performance. The work in this proposal will focus on establishing the feasibility of making a vertical array for studying gene regulation in many cancer samples simultaneously. Potential throughput is very high, such that multiple regions from each tumor can be studied simultaneously. This approach will be useful in confirming that a gene is indeed differentially regulated, in determining the distribution of expression of the gene in the transformed and surrounding normal tissue, and in determining whether the gene behaves in a similar manner in different cases of the same type of cancer and in different kinds of cancer. The goals require extensive and efficient microdissection, and we have built a novel instrument, the "tissue mill," to achieve these ends. Relevance: Biomarkers are useful for diagnosis, prognosis, and as potential therapeutic targets for cancer. There are hundreds of potential biomarkers, but further validation is needed before they can be exploited.