Influence of a novel polymorphism in the 3’ untranslated region of the gene PLK1 upon PLK1 mRNA expression and survival of patients with renal cell carcinoma

Abstract

22005 Background: Polo-like kinases (PLK) belong to the family of serine/threonine kinases. They regulate the transit from the G2 phase to mitosis during the cell cycle. PLK1 is overexpressed in human tumors which correlates with cancer progression. Novel PLK1-inhibitors were developed to improve the efficacy of standard chemotherapeutics which interfere with the cell cycle. Because genetic polymorphisms can influence the transcription of genes, the importance of an A>G single nucleotide polymorphism (SNP) in the 3’ untranslated region (3’UTR) of PLK1 was examined for PLK1 expression and survival for patients with clear cell renal cell carcinoma (RCC). Methods: The examinedtumor collective comprised 141 patients who were treated for RCC at the Department of Urology of the University Hospital of Essen, Germany. DNA was genotyped using the restriction fragment length polymorphism method (RFLP). Kaplan- Meier plots and the log-rank test for trend were used to detect a potential association of overall survival with the 3’UTR SNP. To determine potential genotype-dependent mRNA expression quantitative real-time PCR (qRT-PCR) was applied. Results were compared using ANOVA. Results: Genotyping of the RCC collective showed that 41.1% of the patients were homozygous for the A-allele, 49.6% were homozygous for the G-allele and 9.3% were heterozygous. Acorrelation between the 3’UTR-polymorphism in PLK1 and overall survival was detected showing reduced overall survival for patients carrying the G allele (p=0.009). qRT-PCR analysis showed an increased mRNA expression of PLK1 associated with the G- allele compared to the A allele in tumor tissue from patients with RCC. Conclusion: It has already been described that PLK1 is overexpressed in human tumors and that the abundance of PLK1 correlates with their malignancy. The results presented here show that the abundance of PLK1 is associated with genotypes of the polymorphic 3’UTR. PLK1 genotypes could be a marker for survival of patients with RCC and could potentially be used to identify responders to PLK1 inhibitors. No significant financial relationships to disclose.