EARLY DIAGNOSIS OF CANCER: THE CANFIND CONSORTIUM

癌症成功治疗的一个无可争辩的关键是早期诊断。这有力地证明了参加常规筛查计划的必要性。然而，那些已经到位的制度存在着重大缺陷。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记物的识别，这些标记物可以通过非侵入性方法检测到。这项应用建议识别在早期结肠癌和乳腺癌中过度表达的分泌型和细胞表面蛋白。我们将从一个高度复杂的cDNA文库中提取代表分泌和细胞表面蛋白(秘密)的序列，并使用强大的生物选择来开始。通过专门关注“交易”的蛋白质，我们极大地限制了必须调查的基因集。通过激光捕获显微切割提纯的肿瘤和正常细胞将用于制备用于DNA微阵列差异表达分析的特异性探针。当与序列信息相结合时，这将创建一个关于结肠和乳腺早期病变中分泌和细胞表面蛋白的表达模式的数据库。这些显示差异表达的克隆将使用RNA微阵列进行肿瘤和组织特异性测试。将根据这些表达模式选择一组潜在的标记。有希望的候选者的DNA序列和免疫探针都将被传递给Marker验证实验室进行进一步评估。

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.