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

2019 ◽  
Vol 24 ◽  
pp. 221-226
Author(s):  
K. V. Onyshchenko ◽  
V. M. Grygorenko ◽  
L. V. Pereta ◽  
Yu. R. Serbai ◽  
T. V. Voitsitskyi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Loss Of Heterozygosity ◽  
Renal Cell ◽  
Clear Cell ◽  
Malignant Tumors ◽  
Polymorphic Information Content ◽  
Methylation Status ◽  
Cell Renal Cell Carcinoma ◽  
Vhl Gene

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.

Rare localization of renal cell carcinoma metastases in the paranasal sinuses and breast: a case report

2019 ◽  
Vol 22 (6) ◽  
pp. 13-22
Author(s):  
E. V. Kryaneva ◽  
N. A. Rubtsova ◽  
A. V. Levshakova ◽  
A. I. Khalimon ◽  
A. V. Leontyev ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Paranasal Sinuses ◽  
Renal Cell ◽  
Clinical Case ◽  
Clear Cell ◽  
Malignant Tumors ◽  
Metastatic Potential ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Lesions

This article presents a clinical case demonsratinga high metastatic potential of clear cell renal cell carcinoma combined with atypical metastases to breast and paranasal sinuses. The prevalence of metastatic lesions to the breast and paranasal sinuses in various malignant tumors depending on their morphological forms is analyzed. The authors present an analysis of data published for the last 30 years. The optimal diagnostic algorithms to detect the progression of renal cell carcinoma and to evaluate the effectiveness of the treatment are considered.

scholarly journals Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma

2008 ◽  
Vol 123 (2) ◽  
pp. 395-400 ◽  
Author(s):  
Jean-Jacques Patard ◽  
Patricia Fergelot ◽  
Pierre I. Karakiewicz ◽  
Tobias Klatte ◽  
Quoc-Dien Trinh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Aggressiveness ◽  
Poor Survival ◽  
Cell Renal Cell Carcinoma ◽  
Vhl Gene ◽  
Caix Expression

scholarly journals Vhl Dependent Expression of REDD1 and PDK3 Proteins in Clear-Cell Renal Cell Carcinoma

2018 ◽  
Vol 37 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Bojana B. Ilic ◽  
Jadranka A. Antic ◽  
Jovana Z. Bankovic ◽  
Ivana T. Milicevic ◽  
Gordana S. Rodic ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Linear Regression Analysis ◽  
Multivariate Linear Regression Analysis ◽  
Cell Renal Cell Carcinoma ◽  
Vhl Gene ◽  
Control Tissue ◽  
Mutational Status

SummaryBackground: Sporadic clear-cell renal cell carcinoma (ccRCC) is associated with mutations in the VHL gene, upregulated mammalian target of rapamycin (mTOR) activity and glycolytic metabolism. Here, we analyze the effect of VHL mutational status on the expression level of mTOR, eIF4E-BP1, AMPK, REDD1, and PDK3 proteins. Methods: Total proteins were isolated from 21 tumorous samples with biallelic inactivation, 10 with monoallelic inactivation and 6 tumors with a wild-type VHL (wtVHL) gene obtained from patients who underwent total nephrectomy. The expressions of target proteins were assessed using Western blot. results: Expressions of mTOR, eIF4EBP1 and AMPK were VHL independent. Tumors with monoallelic inactivation of VHL underexpressed REDD1 in comparison to wtVHL tumors (P = 0.042), tumors with biallelic VHL inactivation (P < 0.005) and control tissue (P = 0.004). Additionally, REDD1 expression was higher in tumors with VHL biallelic inactivation than in control tissue (P = 0.008). Only in wt tumor samples PDK3 was overexpressed in comparison to tumors with biallelic inactivation of VHL gene (P = 0.012) and controls (P = 0.016). In wtVHL ccRCC, multivariate linear regression analysis revealed that 97.4% of variability in PDK3 expression can be explained by variations in AMPK amount. Conclusion: Expressions of mTOR, eIF4EBP1 and AMPK were VHL independent. We have shown for the first time VHL dependent expression of PDK3 and we provide additional evidence that VHL mutational status affects REDD1 expression in sporadic ccRCC.

scholarly journals LncRNA DGCR5 Isoform-1 Silencing Suppresses the Malignant Phenotype of Clear Cell Renal Cell Carcinoma via miR-211-5p/Snail Signal Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Guang-Xin Zhong ◽  
Dan Luo ◽  
Yi-jun Fan ◽  
Jue Wang ◽  
Bing-Qiang Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Malignant Tumors ◽  
Quantitative Polymerase Chain Reaction ◽  
Promoting Effect ◽  
Cell Renal Cell Carcinoma ◽  
Mesenchymal Transition ◽  
Snail Protein

Long non-coding RNAs (lncRNAs) play important roles during the initiation and progression of cancer. We identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a clear cell renal cell carcinoma (ccRCC) cancer- and lineage-specific lncRNA. Agarose gel electrophoresis analysis and sanger sequencing verified two main isoforms of DGCR5 in ccRCC patient tissues and cell lines. Quantitative polymerase chain reaction further demonstrated that the expression level of DGCR5 major isoform (isoform-1) was higher in ccRCC tissues than that in papillary/chromophobe RCC and other multiple solid malignant tumors. We investigate the biological functions of DGCR5 isoform-1 in ccRCC and show that DGCR5 isoform-1 exerts a tumor-promoting effect in ccRCC. DGCR5 isoform-1 is localized in cytoplasm and shares the same binding sequence to the tumor-suppressive miR-211-5p with the epithelial-to-mesenchymal transition key component SNAI. Furthermore, cellular and molecular experiments demonstrate that DGCR5 isoform-1 could sequester miR-211-5p, leading to the elevation of Snail protein and downregulation of its downstream targets and further promoting ccRCC cell proliferation and migration. Thus, our study indicates that DGCR5 isoform-1 could contribute to ccRCC progression by sponging miR-211-5p through regulating the expression of Snail protein and could serve as a reliable diagnostic biomarker in ccRCC.

VHL Gene Alterations in Italian Patients with Isolated Renal Cell Carcinomas

2013 ◽  
Vol 28 (2) ◽  
pp. 208-215 ◽  
Author(s):  
Lucia Anna Muscarella ◽  
Leonardo D'Agruma ◽  
Annamaria la Torre ◽  
Maddalena Gigante ◽  
Michelina Coco ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Loss Of Heterozygosity ◽  
Renal Cell ◽  
Malignant Neoplasm ◽  
Suppressor Gene ◽  
Cell Renal Cell Carcinoma ◽  
Vhl Gene ◽  
Vhl Disease ◽  
Gene Alterations

Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm of the kidney and belongs to the few human tumors known to develop from mutations of the VHL tumor suppressor gene. VHL germline mutations are associated with hereditary ccRCCs in VHL disease. However, somatic VHL gene defects may also occur in sporadic ccRCCs. In this study, we analyzed the frequency and the spectrum of VHL gene alterations in 35 Italian patients with sporadic renal cell carcinoma (RCC). Tumor-specific intragenic VHL pathogenic mutations were detected in 38% (11/29) of the ccRCC patients and 33% (2/6) of the patients with other types of RCC. One novel 18-bp in-tandem duplication and 4 previously unreported nucleotide changes in the VHL gene were described. Microsatellite analysis showed loss of heterozygosity for at least 1 informative marker in 43% (9/21) of the ccRCCs and 50% (3/6) of the non-ccRCCs; 5 of the 13 tumors (38%) harboring VHL gene alterations also had loss of heterozygosity for at least 1 microsatellite marker. Our results confirm that somatic inactivation of the VHL gene may play a pivotal role in the tumorigenesis of sporadic ccRCCs in Italian patients and suggests that mutation analysis of the VHL gene may be helpful for discriminating sporadic, VHL-gene-related ccRCCs from those related to VHL disease.

Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 424-424
Author(s):  
Seung-Kwon Choi ◽  
Joong Geun Lee ◽  
Koo Han Yoo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Survival Curve ◽  
Methylation Status ◽  
Clinicopathological Parameters ◽  
Cell Renal Cell Carcinoma ◽  
Value Differences ◽  
Normal Tissues

424 Background: The high-throughput method using microarray is easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. Methods: The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. Results: We identified two genes (HOXA5 and MSH2) with β-value differences of more than 0.3 between cancer and normal tissues. High methylation group in HOXA5 had high Fuhrman’s nuclear grade (P=0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P>0.05). Survival curve of high methylation group in HOXA5 was slightly lower than that of low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P>0.05). Conclusions: We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma.

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