NDLI: Resequencing of the vascular endothelial growth factor promoter reveals haplotype structure and functional diversity

Content Provider	Springer Nature Link
Author	Radovich, Milan Hancock, Bradley A. Kassem, Nawal Mi, Deming Skaar, Todd C. Schneider, Bryan P.
Copyright Year	2010
Abstract	Our group has previously reported that SNPs in the VEGF promoter are strongly associated with efficacy and toxicity to the anti-VEGF antibody bevacizumab in breast cancer. In order to better understand the biologic mechanism for our previously reported biomarkers, we embarked on a comprehensive evaluation of genetic variation in the VEGF promoter coupled with a study of its intrinsic function. We resequenced 48 Caucasians and 48 African-Americans for the VEGF promoter to identify SNPs and elucidate its haplotype structure. We further cloned the haplotypes into reporter constructs and assessed the role of SNPs on promoter function in breast cancer cell lines. SNPs that were identified included twenty previously reported SNPs/insertions/deletions, one novel SNP, and one novel deletion. Among these variants, we identified five SNPs that tag six haplotypes capturing 74% of the genetic variation of the promoter. Subsequently, assessment of the haplotypes in reporter constructs demonstrates significant variation in promoter induced expression among the haplotypes. In particular, two haplotypes had higher expression and one haplotype had lower expression across cell lines. Haplotypes containing SNPs previously reported to be associated with increased survival with the use of bevacizumab are high-expressing haplotypes, thus lending putative functional evidence to the prior clinical finding.
Starting Page	211
Ending Page	218
Page Count	8
File Format	PDF
ISSN	09696970
Journal	Angiogenesis
Volume Number	13
Issue Number	3
e-ISSN	15737209
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-06-16
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Haplotype Promoter Resequencing SNP VEGF Oncology Ophthalmology Cardiology Cell Biology Biomedicine general Cancer Research
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Cancer Research

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