Functional genomics of cancer

癌症的功能基因组学

• 批准号: 6830483
• 负责人: PAUL S. MELTZER
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 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/6830483
• 关键词: biotechnology; breast neoplasms; chromosome aberrations; complementary DNA; estrogen receptors; fluorescent dye /probe; functional /structural genomics; gene expression; gene mutation; genetic models; human subject; melanoma; metastasis; microarray technology; neoplasm /cancer genetics; neoplastic cell; pediatric neoplasm /cancer; robotics; sarcoma; statistics /biometry

One of the major problems in cancer biology is to define the aberrant pattern of gene expression in tumor cells and to relate this pattern to specific genomic alterations which occur during tumorigenesis. To address this issue, a novel technology, cDNA microarray hybridization is being applied to analyze the consequences of chromosome anomalies at the level of gene expression. Using a robotic device, it is possible to print thousands of DNA clones representing thousands of genes on a single microscope slide. Fluorescent probes prepared from any cell or tissue source of interest are then hybridized to these arrays providing a large scale view of gene expression. The ultimate goal of this project is genome wide expression analysis. In this fashion, it is proving possible to profile individual diseases, and to determine the consequences of a given genetic alteration on gene expression. This technology is now being applied in model systems carrying alterations in tumor specific genes affected by translocation, activation mutation, amplification or deletion, and in models which have distinct biological properties such as metastasis or responsiveness to hormones. Information obtained from model systems is then integrated with gene expression profiles derived from the statistical analysis of expression data from tissue specimens. Our recent efforts have applied this technology to pediatric cancers, adult sarcomas, melanoma and breast cancers. We have been able to establish the potential of microarrays for the accurate diagnosis of pediatric cancers and for distinguishing estrogen receptor positive breast cancers from receptor negative tumors. Using data from laboratory models we have uncovered patterns of gene expressionrelated to important clinical properties of cancers such as estrogen sensitivity in breast cancer and metastasis in melanoma and osteosarcoma.

癌症生物学的主要问题之一是定义肿瘤细胞中基因表达的异常模式，并将这种模式与肿瘤发生过程中发生的特定基因组改变联系起来。为了解决这个问题，一种新的技术，正在应用cDNA微阵列杂交来分析基因表达水平上染色体异常的后果。使用机器人装置，可以在单个显微镜载玻片上打印成千上万个代表数千个基因的DNA克隆。然后将来自任何细胞或组织来源制备的荧光探针与这些阵列杂交，从而提供了大规模的基因表达视图。该项目的最终目标是基因组广泛的表达分析。以这种方式，证明可以介绍个体疾病，并确定给定遗传改变对基因表达的后果。现在，该技术应用于模型系统中，该模型系统携带受易位，激活突变，扩增或缺失影响的肿瘤特异性基因的变化，以及具有不同生物学特性（例如转移或对激素反应性）的模型。然后将从模型系统获得的信息与从组织样品的表达数据统计分析得出的基因表达谱集成。我们最近的努力将这项技术应用于小儿癌，成人肉瘤，黑色素瘤和乳腺癌。我们已经能够建立微阵列的潜力，以准确诊断儿科癌症，并区分雌激素受体阳性乳腺癌和受体阴性肿瘤。使用实验室模型的数据，我们发现了与乳腺癌和黑色素瘤和骨肉瘤中雌激素敏感性等癌症的重要临床特性相关的基因表达模式。