Genetic and epigenetic alterations of VHL gene in clear cell renal cell carcinoma

  • K. V. Onyshchenko
  • V. M. Grygorenko
  • L. V. Pereta
  • Yu. R. Serbai
  • T. V. Voitsitskyi
  • I. Ya. Skrypkina


Aim. Renal cell carcinomas (RCC) – cancerous neoplasms of the genitourinary system representing about 3% of human malignant tumors. For malignancy degree indexing and tumor typing, shape of cell nucleus is widely used. However, genetic changes, in particular inactivation of von Hippel-Lindau (VHL) gene can serve as indicators of RCC progression. Thus, the purpose of our study was establishing the methylation status and loss of heterozygosity of the VHL gene as a potential and applicable clinical marker of kidney tumors. Methods. Determination of allelic imbalance in VHL gene expression was performed by PCR of STR-markers with subsequent fragments separation in 8% PAAG and by capillary gel electrophoresis of fluorescent-labeled PCR fragments. Methyl-specific PCR was used for epigenetic variability of VHL gene promoter. To detect statistically significant differences between tumor specimens and adjacent kidney tissues, Fisher's exact test and Mann-Whitney U-criterion were applied. Results. In 57% of the tumor samples for the marker D3S1038 and 48% for the D3S1317 loss of heterozygosity of the VHL gene was detected. Polymorphic information content for these loci was 84% for D3S1038 and 90% for D3S1317. The VHL promoter hypermethylation was 77%. Conclusions. The obtained results indicate that VHL gene can be reviewed as a candidate for not only diagnostic, but also prognostic application in RCC cancer.

Keywords: clear cell renal cell carcinoma, epigenetic changes, methylation, loss of heterozygosity, VHL.


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