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.
| Trautmann, Karolin; Terdiman, Jonathan P; French, Amy J et al. (2006) Chromosomal instability in microsatellite-unstable and stable colon cancer. Clin Cancer Res 12:6379-85 |
| Mehta, Kshama R; Nakao, Kentaro; Zuraek, Marlene B et al. (2005) Fractional genomic alteration detected by array-based comparative genomic hybridization independently predicts survival after hepatic resection for metastatic colorectal cancer. Clin Cancer Res 11:1791-7 |
| Devries, Sandy; Nyante, Sarah; Korkola, Jim et al. (2005) Array-based comparative genomic hybridization from formalin-fixed, paraffin-embedded breast tumors. J Mol Diagn 7:65-71 |
| Nakao, Kentaro; Mehta, Kshama R; Fridlyand, Jane et al. (2004) High-resolution analysis of DNA copy number alterations in colorectal cancer by array-based comparative genomic hybridization. Carcinogenesis 25:1345-57 |
