Lymph node involvement is one of the most important clinical features to determine when managing colorectal cancer patients. Node-negative disease is often cured by surgery alone, whereas node-positive disease requires the administration of chemotherapy, and is associated with a decreased probability of cure. We have identified alterations to the p arm of chromosome 8, and gene expression changes which are correlated with positive lymph node status. This application seeks to determine if mutations in a novel 8p tumor suppressor gene, along with resulting gene expression alterations, are associated with recurrence among node-negative colorectal cancer patients. If successful, these tests will lead to improved ability to diagnose node-positive disease, and will significantly impact the clinical decisions made during the management o early stage colorectal cancer patients.

Public Health Relevance

Patients with node-negative colorectal cancers can usually be cured by surgery alone, while patients with node-positive disease require additional chemotherapy or radiation therapy. The diagnosis of node-negative disease is sometimes wrong, and some patients are mistakenly undertreated. This application seeks to define the mechanism by which mutations in a novel tumor suppressor gene can cause colorectal cancers to metastasize to the regional lymph nodes. This will lead to genetic testing of tumors to prevent the accidental diagnosis of benign disease, and ultimately to novel strategies to manage patients with metastatic colorectal cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA127683-01A2
Application #
7739814
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Thurin, Magdalena
Project Start
2009-05-15
Project End
2010-04-30
Budget Start
2009-05-15
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$156,200
Indirect Cost
Name
University of South Carolina at Columbia
Department
Pathology
Type
Schools of Medicine
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208
Shull, Austin Y; Clendenning, Megan L; Ghoshal-Gupta, Sampa et al. (2013) Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1) gene reveals association with early age of diagnosis in colorectal cancer patients. PLoS One 8:e58731
Meeh, Paul F; Farrell, Christopher L; Croshaw, Randal et al. (2009) A gene expression classifier of node-positive colorectal cancer. Neoplasia 11:1074-83