Genomic Markers of Colon Cancer Progression

描述：（由申请人提供）本项目的目标是确定 并验证与侵袭性肿瘤行为相关的肿瘤标志物， 并预测结肠癌患者的预后。DNA拷贝数 将使用高通量以百万分之一的分辨率识别改变 基于阵列的计算全息图。将根据与以下方面的关联来识别变更： 临床结果。将使用多组肿瘤来鉴定基因组 改变与结果相关的区域：来自UCSF的新鲜肿瘤 和CHTN组织库（一个试点项目，用于完善其余项目中使用的阵列） 研究），来自UCSF的存档未治疗淋巴结阴性肿瘤，存档治疗 来自UCSF的淋巴结阳性肿瘤，以及来自三个不同国家的肿瘤 临床试验我们将测试相同的基因组改变是否 预测每个组的结果。总共有超过1200个肿瘤 在这项研究中，基因组改变的特征，一些提供 有足够的能力检测风险差异， 做出关于治疗的临床决定。 CGH阵列将应用于来自患者的肿瘤材料， 在同类临床试验中治疗。这些研究将利用 正在进行的相关科学研究与三个独立的 治疗试验1)将通过以下方式检测候选标记物的预测效用： 在接受佐剂的一组300个III期肿瘤中的DNA阵列分析 化疗（CALGB 9865/8896）。这些案件的结果是已知的， 确定了微卫星不稳定状态; 2）候选 预后基因组标记将通过DNA阵列分析在一组 300例仅接受手术切除的II期结肠癌（CALGB 9581).这些病例目前正在累积，表型标记正在 评估。3)候选预测基因组标记将通过DNA阵列检测 一组300例接受手术切除的III期结肠癌的分析 和两种辅助疗法之一（CALGB 89803）。这些案件也被 累积，并评估表型标志物。

DESCRIPTION: (Provided by applicant) The goal of this Project is to identify and validate tumor markers which are associated with aggressive tumor behavior, and which predict the outcome of patients with colon cancer. DNA copy number alterations will be identified at megabase resolution using high throughput array-based CGH. Alterations will be identified based on associations with clinical outcome. Multiple sets of tumors will be used to identify genomic regions whose alteration is associated with outcome: fresh tumors from the UCSF and CHTN tissue banks (a pilot set to refine the arrays used in the remaining studies), archival untreated node negative tumors from UCSF, archival treated node positive tumors from UCSF, and tumors from three separate national clinical trials. We will test whether the same genomic alterations are predictive of outcome in each of these groups. A total of over 1200 tumors will be characterized for genomic alterations in this study, a number providing sufficient power to detect differences in risk to allow patients and physicians to make clinical decisions about therapy. CGH arrays will be applied to tumor material from patients who have been treated on homogeneous clinical trials. These studies will take advantage of ongoing correlative science studies which are associated with three separate treatment trials. 1) Candidate markers will be tested for predictive utility by DNA array analysis in a set of 300 stage III tumors receiving adjuvant chemotherapy (CALGB 9865/8896). Outcome for these cases is already known, and the status of microsatellite instability has been defined, 2) Candidate prognostic genomic markers will be detected by DNA array analysis in a set of 300 Stage IIcolon cancers undergoing surgical resection alone (CALGB 9581).These cases are currently being accrued, and phenotypic markers are being assessed. 3) Candidate predictive genomic markers will be detected by DNA array analysis in a set of 300 Stage III colon cancers undergoing surgical resection and one of two adjuvant therapies (CALGB 89803). These cases are also being accrued, and phenotypic markers assessed.