Genomics

Dataset Information

36

Genome-wide SNP array data from Human Variation Panel by Illumina 510S


ABSTRACT: Radiation therapy is used to treat half of all cancer patients. Response to radiation therapy varies widely among patients. Therefore, we performed a genome-wide association study (GWAS) to identify biomarkers to help predict radiation response using 277 ethnically defined human lymphoblastoid cell lines (LCLs). Basal gene expression levels (Affymetrix) and 1.3 million genome-wide SNP markers (Illumina) were assayed for all 277 human LCLs. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays for radiation cytotoxicity were also performed to obtain area under the curve (AUC) as a radiation response phenotype for use in the association studies. Functional validation of candidate genes, selected from an integrated analysis that used SNP, expression and AUC data, was performed with multiple cancer cell lines using specific siRNA knockdown, followed by MTS and colony-forming assays. 27 loci, each containing at least 2 SNPs within 50kb with p-values <10-4, were associated with radiation AUC. 270 expression probe sets were associated with radiation AUC with p<10-3. The integrated analysis identified 50 SNPs in 14 of the 27 loci that were associated with both AUC and the expression of 39 genes that were also associated with radiation AUC (p<10-3). Functional validation using siRNA knockdown in multiple tumor cell lines showed that C13orf34, MAD2L1, PLK4, TPD52 and DEPDC1B each significantly altered radiation sensitivity in at least 2 cancer cell lines. Studies performed with LCLs can help to identify novel biomarkers that might contribute to variation in response to radiation therapy and enhance our understanding of mechanisms underlying that variation. Overall design: EBV-transformed LCLs from 96 African-American (AA), 96 Caucasian-American (CA), and 96 Han Chinese-American (HCA) unrelated healthy subjects (sample sets HD100AA, HD100CAU, HD100CHI) were purchased from the Coriell Cell Repository (Camden, NJ).

INSTRUMENT(S): Illumina HumanExon510-Sv1 DNA Analysis BeadChip (HumanExon510Sv1_D)

ORGANISM(S): Homo sapiens  

SUBMITTER: Liewei Wang  

PROVIDER: GSE24245 | GEO | 2010-09-25

SECONDARY ACCESSION(S): PRJNA133737

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
GSE24245_510_intensities.csv.gz Csv
GSE24245_510_processed.csv.gz Csv
GSE24245_RAW.tar Raw
filelist.txt Txt
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