MOLECULAR MARKERS FOR METASTASIS OF COLORECTAL CANCER

接受根治性手术切除的患者的不良结局 直肠和结肠癌是由于局部复发或出现 最初是隐匿性远处转移。 分子方法学提供了新的 评估切缘状态和转移的方法 原发性肿瘤中的表型。 聚合酶链反应与克隆入 用于进一步扩增的噬菌体载体允许检测来自 在成千上万的非肿瘤细胞中发现一个突变癌细胞。 代表性差异分析（RDA）提供了识别 并表征可能是肿瘤预后标志物的扩增。 本项目中要检验的假设是： L.显微镜下手术切缘的隐匿性肿瘤细胞 直肠癌患者可以通过分子遗传分析检测， 从而用作复发的标记。 2.原发性结直肠癌中的扩增基因是低分化的标志物 预后 本项目的具体目标是： L.评估边缘组织和盆腔组织中ras和p53基因的突变 直肠根治性切除术后收集的冲洗标本 癌 分子遗传学结果将与组织病理学相关 结果、复发和生存率。 2.将代表性差异分析（RDA）应用于配对的 转移性和非转移性原发性结肠直肠癌。 RDA探针 检测扩增将被克隆，映射，并用于搜索 靶基因 扩增将作为预后标志物进行评价。

Adverse outcome in patients who undergo curative surgical resection of rectal and colonic carcinoma results from local recurrence or emergence of initially occult distant metastases. Molecular methodologies offer new approaches to evaluate the status of resection margins and the metastatic phenotype in primary tumors. Polymerase chain reaction with cloning into bacteriophage vectors for further expansion permits detection of DNA from one mutant cancer cell among thousands of non-neoplastic cells. Representational difference analysis (RDA) provides the ability to identify and characterize amplifications which may be prognostic markers in tumors. The hypotheses to be tested in this project are: l. Microscopically occult neoplastic cells at the surgical margins of rectal cancer patients can be detected by molecular genetic analysis, thereby serving as markers for recurrence. 2. Amplified genes in primary colorectal carcinomas are markers for poor prognosis. Our specific aims for this project are to: l. Evaluate mutations in ras and p53 genes in margin tissue and pelvic irrigation specimens collected after curative resection of rectal carcinomas. Molecular genetic results will be related to histopathologic findings, recurrence, and survival. 2. Apply representational difference analysis (RDA) to pairs of matched metastatic and non-metastatic primary colorectal carcinomas. RDA probes detecting amplifications will be cloned, mapped, and used to search for target genes. The amplifications will be evaluated as prognostic markers.