Dinucleotide-barcode reporter assay of breast risk variants identified PAX9 as a gene promoting breast cancer procession

We adapted the DiR barcode-based parallel reporter assay systems strategy to systematically identify the breast cancer related SNPs that affect gene expression by modulating activities of regulatory elements. Among 293 SNPs linked with GWAS-identified breast cancer-risk SNPs, we found seven functional regulatory SNPs in MCF7 cells. Further mechanism study indicates that one SNP regulates gene expression in breast cancer malignancy. The DiR system has great potential to advance the functional study of risk SNPs that have associations with polygenic diseases. Our findings hold great promise in benefiting breast cancer patients with prognostic prediction. Overall design: SNP DiR-seq report analysis in MCF7, ZR-75-1, MDA-MB-453, BT-20, BT-474, MDA-MB-468, T-47D, SK-BR-3 and BT-549 (3 independent replicates, respectively), Input plasmid library before transfection (2 independent replicates in MCF7 cell, 3 independent replicates other eight cell lines).