Melanoma is a rare, albeit potentially highly aggressive malignant tumor of melanocytes. Melanomas can spread quickly beyond the primary site at which they developed, they are highly curable if discovered and treated early. Primary tumor thickness has been considered to be the most influential prognostic factor in melanoma patients. No previous studies have reported an association between single nucleotide polymorphisms(SNPs) and tumor thickness or the biological roles of SNPs in melanoma progression. To determine whether common genetic variants that influence tumor thickness affect melanoma prognosis and also elucidate the molecular mechanism of disease progression, we propose to perform a coordinated genome-wide SNP analysis together with targeted gene expression analysis. We will test our hypothesis through the following aims: 1)To determine common genetic variants associated with Breslow tumor thickness among melanoma patients using genome-wide SNP analysis;2)To examine expression patterns of candidate genes identified in Aim 1 using patient tissues with varying tumor thickness categories, via mRNA expression analysis and immunohistochemistry;and 3)To predict risk of melanoma recurrence and death on the basis of the SNPs identified in Aim 1. Identifying common genetic determinants of tumor thickness may provide new insights into prognosis in melanoma. Our findings will have a significant impact on the staging of melanoma and outcome prediction for melanoma patients who are at risk for relapse and metastasis, and provide clues for the development of new molecular targeted therapies.

Public Health Relevance

No previous studies have reported an association between single nucleotide polymorphisms and tumor thickness or the biological roles of SNPs in melanoma progression. This application is to determine whether common genetic variants that influence tumor thickness affect melanoma prognosis and also elucidate the molecular mechanism of disease progression. Then we can apply these biomarkers to clinical practice.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA173792-02
Application #
8598826
Study Section
Special Emphasis Panel (ZCA1-SRLB-D (O1))
Program Officer
Elena, Joanne W
Project Start
2013-01-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
2
Fiscal Year
2014
Total Cost
$71,100
Indirect Cost
$26,100
Name
University of Texas MD Anderson Cancer Center
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030