Targeted Single Nucleotide Polymorphisms (SNPs) to Classify Subtypes of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Transplant.
- To determine and define the biological basis of different subtypes of chronic
graft-vs-host disease using a targeted single nucleotide polymorphisms approach in
patients who have undergone allogeneic stem cell transplantation.
OUTLINE: Two important aspects of the methodologies that will be employed for the analysis
of SNPs associated with GVHD are throughput efficiency to be able to perform the assays on a
reasonable number of samples as well as having the ability to add or remove SNPs to the
assay panel. While a genome-wide association study to identify variants associated with GVHD
would offer an unbiased approach, our patient cohort size would not allow significant
statistical power in the study. Therefore, a more targeted approach using two established
technologies is proposed.
The Sequenome assay uses the unique combination of a single-base primer extension assay
incorporating one of four modified nucleotides. The four modified nucleotides each have a
unique mass that allows them to be distinguished from one another using mass spectrometry.
Each SNP is determined analyzing the primer extension product from a PCR amplicon that
surrounds the SNP of interest. The development of each assay involves designing flanking PCR
primers and an internal extension assay using web-based software provided by Sequenome. The
assays can be designed to analyze up to 30 SNPs in a single reaction, providing a
customizable, efficient and high-throughput assay for SNPs of interest.
Observational Model: Case-Only, Time Perspective: Retrospective
To study the SNP profiles of a select group of candidate non-HLA genes among various cGVHD subtypes. Patients will be stratified as having classic cGVHD vs. non-classic GVHD for initial analyses.
Upon data collection of final patient
Madan Jagasia, MD
Vanderbilt-Ingram Cancer Center
United States: Federal Government
VICC BMT 0867
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Nashville, Tennessee 37064|
|Vanderbilt-Ingram Cancer Center at Franklin||Nashville, Tennessee 37064|