Abstract
Abstract Anti-angiogenic therapy to block and disrupt tumor angiogenesis has been used in clinical treatment of various malignancies including: glioblastoma, colorectal, lung and kidney cancer. Currently, the most clinically effective anti-angiogenic agents are the humanized monoclonal antibody (bevacizumab) against vascular endothelia growth factor (VEGF) and the small molecule receptor-tyrosine-kinase inhibitors (RTKIs) of VEGF receptors. However, the therapeutic benefit varies substantially for many of these agents. Predictive biomarkers that are required for personalized treatment with these agents are currently not available. Recently the role of germline single-nucleotide polymorphisms (SNPs) has been investigated as potential biomarkers for anti-angiogenic treatments. The rationale is that these agents target the vasculature in host (vessels) rather than tumor tissue, which could mean that much of the variability is dictated by the host. Several studies reported the association of SNPs in VEGFA with differential outcomes from clinical trials with these agents. SNP genotyping assays in these studies used germline DNA extracted from blood. However, collection of peripheral blood is invasive. Saliva and hair that are known to contain genomic DNA can be used as noninvasive and convenient DNA sampling resources, but the limited quantity of DNA in the hair and the low quality of DNA in the saliva make genotyping assays non-reproducible. We have sought to improve SNP genotype assays with DNA from saliva and hair by applying SNP target pre-amplification for genotyping five SNPs (rs699947, rs833061, rs1570360, rs201093, rs3025039) in VEGFA. The concordance of genotyping calls of individual SNP using DNA from blood, saliva and hair from the same volunteer was compared. Our preliminary results demonstrated that pre-amplification substantially improved genotyping calls with saliva DNA and hair DNA samples. The average genotyping call rate with saliva and hair samples was about 45% and 10%, respectively, without pre-amplification. The pre-amplification improved the call rate with saliva and hair samples to 100% and 94%, respectively. The current report may facilitate easier clinical sample collection for genetic tests for these SNPs. Citation Format: Gloria R. Xue, Crystal R. Xue, Fei Shen, Bryan P. Schneider. Potential use of saliva and hair samples to identify genetic markers for anti-VEGF therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5216. doi:10.1158/1538-7445.AM2015-5216
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