Studying Tissue Samples From Patients With Stage II Colon Cancer Treated on Clinical Trial CLB-9581
Recruitment status was Active, not recruiting
RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors understand how patients respond to treatment.
PURPOSE: This laboratory study is looking at tissue samples from patients with stage II treated on clinical trial CLB-9581.
Genetic: gene expression analysis
Genetic: mutation analysis
Genetic: polyacrylamide gel electrophoresis
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: diagnostic laboratory biomarker analysis
Other: immunohistochemistry staining method
|Official Title:||Correlative Science Studies in Colon Cancer a Companion Study to CALGB 9581 and 89803|
- Associate methylated and silenced DNA repair genes, MLH1, WRN, or MGMT, or CIMP colorectal cancers with the clinical endpoints of overall (OS) and disease-free survival (DFS) [ Designated as safety issue: No ]
- DFS [ Designated as safety issue: No ]
- Predictive value of other novel methylated genes indentified through methylation array studies [ Designated as safety issue: No ]
- Correlate CIMP and methylated genes with other genetic alterations and tumor-specific characteristics [ Designated as safety issue: No ]
- MRE11 status of the MSI tumors and correlate with response to the camptothecin-related compound irinotecan [ Designated as safety issue: No ]
|Study Start Date:||July 2007|
- To assess the ability of a prognostic gene expression signature to stratify stage II colorectal cancer patients into those who will experience relapse within five years post surgery (high risk) and those who will experience five-year disease-free survival (low risk), without additional treatment.
- To correlate the methylation status of the individual genes, MLH1, WRN, and MGMT with survival.
- To correlate the CIMP status (CIMP vs nonCIMP) of the tumors with survival.
- To correlate the expression status of the individual genes based on the immunostaining results with survival.
- To correlate the expression of the functional groups of proteins in which survival is correlated with the expression of the MLH1 functional group (MLH1, PMS2, and MSH2), the WRN functional group (WRN, MRE11, and MLH1), and the MGMT functional group (MGMT, MYH, and OGG) with survival (the loss of expression of any member of each functional group will be scored as indicating loss of function of the functional group).
- To correlate the mutation status of MRE11 in MSI colorectal cancers with disease-free survival and overall survival.
- To define the association of CIMP and methylated genes with other genetic alterations and tumor-specific characteristics.
OUTLINE: This is a multicenter, companion study.
Tissue samples from patients are analyzed for K-ras mutations; COX-2, phospho-AKT, and VEGF overexpression; microvessel density; association of genomic instability with microsatellite instability and p53 mutations; and methylation status of MLH1, MGMT, and WRN and to identify prognostic biomarkers by LINE-1 hypomethylation, PIK3CA mutation, BRAF mutation, fatty acid sysnthase (FASN) expression, and vitamin D receptor (VDR) expression.Techniques used include immunohistochemistry, PCR, RT-PCR, and gel electrophoresis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00897429
|Study Chair:||Monica M. Bertagnolli, MD||Dana-Farber/Brigham and Women's Cancer Center|