Genomic Variation in Myeloma: Design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression free survival
We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma. We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes.
A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n=70) versus long term progression-free survivors (greater than 3 years, n=73) in two phase III clinical trials.
Results: Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival.
While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes.
Conclusions: A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma.
The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS.
Author: Brian Van Ness, Christine Ramos, Majda Haznadar, Antje Hoering, Jeffrey Haessler, John Crowley, Susanna Jacobus, Martin Oken, Vincent Rajkumar, Philip Greipp, Bart Barlogie, Brian Durie, Michael Katz, Gowtham Atluri, Gang Fang, Rohit Gupta, Michae
Published on: 2008-09-08
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
make sure to read our disclaimer prior to contacting 7thSpace Interactive. To contact our editors, visit our online helpdesk. If you wish submit your own press release, click here.
Social Bookmarking
RETWEET This! | Digg this! | Post to del.icio.us | Post to Furl | Add to Netscape | Add to Yahoo! | Rojo
|
|
