Linked Life Data

20552269

Source:http://linkedlifedata.com/resource/pubmed/id/20552269

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-9-20
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1573-7209
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
211-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Resequencing of the vascular endothelial growth factor promoter reveals haplotype structure and functional diversity.
pubmed:affiliation
Department of Medicine, Division of Hematology, Indiana University School of Medicine, Indianapolis, IN, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural