Genomic Markers of Colon Cancer Progression

描述：(申请人提供)本项目的目标是识别和验证与侵袭性肿瘤行为相关的肿瘤标记物， 并预测结肠癌患者的预后。DNA拷贝数 将使用高吞吐量在兆级分辨率下识别更改 基于数组的计算全息。更改将基于与以下各项的关联来确定 临床结果。多组肿瘤将用于鉴定基因组 改变与预后相关的区域：来自加州大学旧金山分校的新鲜肿瘤 和CHTN组织库(一个试点集，以完善剩余的 研究)，加州大学旧金山分校未治疗的结节阴性肿瘤，档案治疗 来自加州大学旧金山分校的结节阳性肿瘤，以及来自三个不同国家的肿瘤 临床试验。我们将测试同样的基因组变化是否 对每一组的结果进行预测。总共有1200多个肿瘤将 在这项研究中描述了基因组变化的特征，一些提供 足够的能力来检测风险差异，以允许患者和医生 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 在同类临床试验中接受治疗。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)将通过以下方式测试候选标记的预测性用途 300例接受佐剂治疗的III期肿瘤的DNA阵列分析 化疗(CALGB 9865/8896)。这些案件的结果已经知道，并且 已经定义了微卫星不稳定的状态，2)候选 预后基因组标记将通过DNA阵列分析在一组 300例单纯手术切除的II期结肠癌(CALGB 这些病例目前正在累积，表型标记正在 评估过了。3)利用DNA芯片检测候选基因组预测标记 300例Ⅲ期结肠癌手术切除病例分析 和两种辅助疗法之一(CALGB 89803)。这些案件也正在被 累积，并评估表型标记。

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.