Tissue Microarray Design of Genetic Screening Product

基因筛查产品的组织微阵列设计

• 批准号: 6558788
• 负责人: DAVID E KLEINER
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6558788
• 关键词: biomedical resource; biotechnology; breast neoplasm /cancer diagnosis; breast neoplasms; cell line; cellular oncology; colon neoplasms; diagnosis design /evaluation; genetic screening; glioma; human tissue; lung neoplasms; lymphoma; melanoma; microarray technology; molecular oncology; neoplasm /cancer diagnosis; neoplasm /cancer genetics; ovary neoplasms; prostate neoplasms; technology /technique development; tumor antigens

Identifying genes and gene products that are important in tumor cells is a high priority goal of the National Cancer Institute. In order to determine whether a gene of interest is expressed in human malignancy, investigators must be able to evaluate actual tissue samples of human tumors. Unfortunately, access to large numbers of well-characterized human tissue samples is difficult, and there is a large expense for the preparation of glass slides from tumor in order to perform immunohistochemistry or in-situ hybridization. As a partial solution to this problem, pathologists began to combine multiple tissue samples in one tissue block, in order to reduce the histology costs and the time and effort involved to perform the special studies. This technique has been refined to the point where hundreds of tissue samples can be placed in a grid arrangement in a single paraffin tissue block. Investigators in the NHGRI (Kohenen, Kallioniemi and others) demonstrated the utility of large scale tissue microarrays in a seminal paper published in Science. Following a tissue microarray workshop hosted by NCI in Fall, 1999, a steering committee convened with the purpose of establishing a pathology-based tissue microarray core facility. The steering committee is composed of representatives from intramural and extramural NCI and from the NHGRI. This project is a direct outgrowth of the Extraordinary Opportunity to Define the Signatures of Cancer Cells identified in the 2001 Bypass Budget plan. The goals of the first year were to establish a core microarray production facility based on a similar facility in the NHGRI and to create the first mixed tumor microarrays for nationwide distribution. The principle product of the core is a mixed tumor block containing representative samples of the most common epithelial malignancies (breast, colon, lung, prostate, and ovary) as well as samples of melanoma, glioma and lymphoma. A selection of normal tissue and standard cell lines were also to be included to bring the total number of tissue spots to 500. Anonymized human tumor samples are obtained through the CHTN, and this organization will also handle distribution of arrays on glass slides to investigators in the intramural and extramural scientific community. Three sets of 5 multi-tumor arrays have been prepared in the first production year (FY2001), totaling nearly 3000 slides for distribution. The slides are being distributed from CHTN nearly as fast a they are produced. In addition to slide production, the core facility has been engaged in technology development, from the basic histology procedures to array use to large-scale imaging of arrays. In the second production year, the facility plans to hire a second histotechnician, acquire an automated arrayer and to continue production of multi-tumor arrays. Also in production are tissue arrays of the NCI 60 cell line collection (these are the 60 cell lines used by the NCI to perform anti-tumor drug testing) and collaborative projects for specialized tumor blocks for renal cell carcinoma (collaborator, M. Linehan), mesothelioma (collaborator, D. Schrump and D. Bartlett), and hepatocellular carcinoma (S. Thorgeirsson.

识别肿瘤细胞中重要的基因和基因产物是国家癌症研究所的一个高度优先的目标。为了确定一个感兴趣的基因是否在人类恶性肿瘤中表达，研究人员必须能够评估人类肿瘤的实际组织样本。不幸的是，获得大量具有良好特征的人体组织样本是困难的，并且为了进行免疫组织化学或原位杂交，从肿瘤中制备玻璃载玻片需要大量费用。为了部分解决这一问题，病理学家开始将多个组织样本合并在一个组织块中，以减少组织学成本以及进行特殊研究所涉及的时间和精力。这项技术已经改进到可以将数百个组织样本放置在单个石蜡组织块中的网格排列中。NHGRI的研究人员（Kohenen， Kallioniemi和其他人）在《科学》杂志上发表的一篇开创性论文中展示了大规模组织微阵列的实用性。