A single nucleotide variant of human PARP1 determines response to PARP inhibitors

摘要

rs1805414 allele and genotype frequencies from the “1000 genome” project. PARP1 RNAseq levels from 415 patients with breast cancer were obtained from the TCGA and analyzed according to their rs1805414 genotype status. The -axis represents averaged RPKM levels, and the -axis represents the SNP genotype. values were calculated using unpaired two-tailed -test (*  = 0.0409; **  = 0.345; ***  = 0.0194). The secondary structure of WT, SNP variant PARP1, was determined using predicted free energies via thermodynamic methods. The location of the variant nucleotide is indicated by an arrow for each PARP1 polymorphism. Analysis was conducted by mFOLD. We used RNAsnp to produce Dotplots and to show base-pair probabilities corresponding to changes in global regions. A major change in structure associated with change in sequence was determined by the RNAsnp tool between both variants. WT PARP1 represented in green while SNP variant in red. The Ovarian cell lines COV362 (SNP/SNP) and SKOV3 (WT/WT) were harvested and extracted for their total RNA. mRNA levels of endogenous PARP1 were determined by qPCR as compare to β-actin (*  = 0.016).