EARLY DIAGNOSIS OF CANCER: THE CANFIND CONSORTIUM

癌症早期诊断：CANFIND 联盟

• 批准号: 6175299
• 负责人: DAVID H. BEACH
• 金额: $ 65.52万
• 依托单位: GENETICA, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6175299
• 关键词: breast neoplasms; colon neoplasms; cooperative study; diagnosis design /evaluation; early diagnosis; gene expression; genetic library; genetic markers; image processing; in situ hybridization; neoplasm /cancer diagnosis; neoplasm /cancer genetics; nucleic acid quantitation /detection; nucleic acid sequence; subtraction hybridization; tissue /cell culture

One of the undisputed keys to the successful treatment of cancer is early diagnosis. This strongly argues for participation in routine screening programs. However, those that are in place suffer from significant drawbacks. A major thrust of applied cancer research in the coming years will be a search for improved diagnostic methodologies. This will rely on the identification of a novel set of early tumor markers that can be detected through non-invasive approaches. This application proposes to identify secreted and cell surface proteins that are overexpressed in early stage cancers of the colon and breast. We will begin by distilling from a highly complex cDNA library sequences that represent secreted and cell surface proteins (Secrets) using a powerful biological selection. By focussing exclusively on "trafficked" proteins we greatly limit the set of genes that must be surveyed. Tumor and normal cells purified by laser-capture microdissection will be used for the preparation of specific probes for differential expression analysis on DNA microarrays. When coupled with sequence information, this will create a database of expression patterns for secreted and cell surface proteins in early stage lesions of the colon and breast. Those clones that show differential expression will be tested using RNA microarrays for tumor and tissue specificity. A set of potential markers will be chosen based upon these expression patterns. Both the DNA sequences and immunological probes for promising candidates will be passed to the Marker Validation Laboratories for further evaluation.

癌症成功治疗的一个无可争议的关键是早期诊断。 这强烈支持参与常规筛查计划。 然而，现有的措施存在重大缺陷。 未来几年应用癌症研究的一个主要方向将是寻找改进的诊断方法。 这将依赖于一组新的早期肿瘤标志物的鉴定，这些标志物可以通过非侵入性方法检测。 本申请提出鉴定在结肠癌和乳腺癌的早期阶段中过表达的分泌蛋白和细胞表面蛋白。 我们将开始从一个高度复杂的cDNA文库中提取序列，这些序列代表分泌和细胞表面蛋白（Secrets），使用强大的生物选择。 通过专门关注“贩运”蛋白质，我们极大地限制了必须调查的基因组。 通过激光捕获显微切割纯化的肿瘤和正常细胞将用于制备特异性探针，用于DNA微阵列上的差异表达分析。 当与序列信息结合时，这将创建结肠和乳腺早期病变中分泌和细胞表面蛋白表达模式的数据库。将使用RNA微阵列测试显示差异表达的那些克隆的肿瘤和组织特异性。 将基于这些表达模式选择一组潜在的标志物。 有希望的候选物的DNA序列和免疫探针将被传递到标记验证实验室进行进一步评估。