Cancer Vertical Arrays

癌症垂直阵列

• 批准号: 7232454
• 负责人: JOHN T WELSH
• 金额: $ 21.08万
• 依托单位: SIDNEY KIMMEL CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7232454
• 关键词: Behavior; Biological; Biological Markers; Cells; Data; Development; Diagnosis; Dot Immunoblotting; Future; Gene Expression; Gene Expression Regulation; Genes; Glass; Goals; Malignant Neoplasms; Malignant neoplasm of prostate; Messenger RNA; Microdissection; Molecular Biology; Noise; Normal tissue morphology; Numbers; Performance; Population; Printing; Production; RNA; Reporting; Reproducibility; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Signal Transduction; Slide; Spottings; Standards of Weights and Measures; Structure; Time; Tissue Microarray; Tissue Sample; Tissue-Specific Gene Expression; Tissues; Transcript; Validation; Work; cancer type; concept; design; instrument; novel; outcome forecast; response; therapeutic target; tumor

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.

描述（由申请人提供）： 癌症分子生物学的实验挑战之一是评估生物标志物的有效性和通用性。这已经成为一个关键的瓶颈，在生物标志物的发展，从差异基因表达揭示了微阵列研究。在这个提议中，我们提出了使用垂直阵列探索癌症中差异基因表达的概念。垂直阵列同时探索许多生物样品中基因的表达，而标准微阵列一次探索响应于一个生物变量的许多基因的表达。在这方面，垂直阵列就像斑点印迹，但是垂直阵列被打印在载玻片上，使它们具有更好的信噪比，并且，而不是在每个点上点出RNA群体的整个复杂性，RNA群体被分成多个点。这些低复杂度表示具有极好的信噪比性能。这项提案的工作将集中在建立一个垂直阵列的可行性，用于同时研究许多癌症样本中的基因调控。潜在的通量非常高，使得可以同时研究每个肿瘤的多个区域。这种方法将用于确认基因确实受到差异调节，用于确定基因在转化的和周围正常组织中的表达分布，以及用于确定基因在相同类型癌症的不同情况下和在不同种类的癌症中是否以相似的方式表现。这些目标需要广泛和有效的显微切割，我们已经建立了一个新的仪器，“组织磨”，以实现这些目标。相关性：生物标志物可用于诊断，预后，并作为癌症的潜在治疗靶点。有数百种潜在的生物标志物，但在开发之前需要进一步验证。