Open AccessGenetic and epigenetic alterations of VHL gene in clear cell renal cell carcinoma
Author(s) -
Kateryna Onyshchenko,
V. Grygorenko,
L.V. Pereta,
Yu. R. Serbai,
Taras Voitsitskyi,
Inessa Skrypkina
Publication year - 2019
Publication title -
faktori eksperimentalʹnoï evolûcìï organìzmìv
Language(s) - English
Resource type - Journals
eISSN - 2415-3826
pISSN - 2219-3782
DOI - 10.7124/feeo.v24.1105
Subject(s) - loss of heterozygosity , biology , epigenetics , renal cell carcinoma , dna methylation , methylation , cancer research , malignancy , clear cell , kidney cancer , clear cell carcinoma , cancer , gene , carcinoma , microbiology and biotechnology , allele , pathology , gene expression , genetics , medicine
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.