Background: The Polo-like Kinase 1 (PLK1) protein regulates cell cycle progression and is overexpressed in manymalignant tissues. Overexpression is associated with poor prognosis in several cancer entities, whereby expressionof PLK1 shows high inter-individual variability. Although PLK1 is extensively studied, not much is known about thegenetic variability of thePLK1gene. The function of PLK1 and the expression of the corresponding gene could beinfluenced by genomic variations. Hence, we investigated the gene for functional polymorphisms. Such polymorphismscould be useful to investigate whether PLK1 alters the risk for and the course of cancer and they could have an impacton the response to PLK1 inhibitors.

Methods: The coding region, the 5′and 3′UTRs and the regulatory regions ofPLK1were systematically sequenced.We determined the allele frequencies and genotype distributions of putatively functional SNPs in 120 Caucasiansand analyzed the linkage and haplotype structure using Haploview. The functional analysis included electrophoreticmobility shift assay (EMSA) for detected variants of the silencer and promoter regions and reporter assays for a 3′UTR polymorphism.

Results: Four putatively functional polymorphisms were detected and further analyzed, one in the silencer region(rs57973275), one in the core promoter region (rs16972787), one in intron 3 (rs40076) and one polymorphism in the3′untranslated region (3′UTR) ofPLK1(rs27770). Alleles of rs27770 display different secondary mRNA structures andshowed a distinct allele-dependent difference in mRNA stability with a significantly higher reporter activity of theA allele (p < 0.01).

Conclusion: The present study provides evidence that at least one genomic variant ofPLK1has functional propertiesand influences expression ofPLK1.This suggests polymorphisms of thePLK1gene as an interesting target for furtherstudies that might affect cancer risk, tumor progression as well as the response to PLK1 inhibitors.