Unique molecular alteration patterns in von Hippel-Lindau (VHL) gene in a cohort of sporadic renal cell carcinoma patients from Pakistan

Khaliq, Shagufta; Ajaz, Sadia; Firasat, Sadaf; Shahid, Saba; Hasan, Asad Shahzad; Sultan, Gauhar; Mohsin, Rehan; Hashmi, Altaf; Mubarak, Muhammed; Naqvi, Syed Arsalan Ahmed; Rizvi, Syed Adib-ul-Hasan; Mehdi, S. Qasim; Abid, Aiysha

doi:10.1016/j.mrfmmm.2014.03.008

Cited by 6 publications

(8 citation statements)

References 21 publications

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“…The condition of VHL promoter methylation has been reported in various cancers, including papillary thyroid carcinoma [35], RCC [36], and colorectal cancer [37]. However, we found that the reported frequency of VHL promoter methylation in RCC is still controversial, with a range from 0% [38] to 35.3% [20]. Therefore, the present meta-analysis was performed to further validate the relationship between VHL promoter hypermethylation and RCC.…”

Section: Discussionmentioning

confidence: 82%

“…Eventually, thirteen eligible studies with 1,998 RCC patients and 294 controls were included in our study (Fig. 1) [20][21][22][23][24][25][26][27][28][29][30][31][32]. Seven of these studies, including 596 RCC patients and 294 nonmalignant samples, evaluated the association of VHL promoter hypermethylation with RCC risk.…”

Section: Basic Characteristics Of the Included Studiesmentioning

confidence: 99%

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The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis

Yang

Zhao²,

Zhao³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC. Methods: The potential relevant papers were searched via PubMed, Embase, EBSCO, CNKI, and Wanfang databases. The overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the relationship between VHL promoter hypermethylation and RCC. Results: Finally, a total of 1,998 RCC patients and 294 controls from 13 eligible articles were included in this meta-analysis. Under the fixed-effects model, the pooled OR from seven studies including 596 RCC and 294 nonmalignant samples showed that VHL promoter hypermethylation was significantly higher in cancer than in controls (OR = 7.93, 95% CI = 2.84- 22.15, P < 0.001). Subgroup analysis based on ethnic population and testing method revealed that hypermethylated VHL had a significantly similar OR value in different races and detection methodologies. No significant association was found between hypermethylated VHL and tumor grade, tumor stage, tumor size, histological types, and lymph node status in cancer (all P > 0.05). In the current study, there was no evidence of publication bias as determined by Egger's test (all P > 0.05). Conclusions: In the investigated patients, VHL promoter hypermethylation, which may play an important role in carcinogenesis of RCC, is significantly associated with an increased risk of RCC. However, VHL promoter hypermethylation is not correlated with specific clinicopathological characteristics. Additional future studies are needed to confirm our results.

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Section: Discussionmentioning

confidence: 82%

Section: Basic Characteristics Of the Included Studiesmentioning

confidence: 99%

The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis

Yang

Zhao²,

Zhao³

et al. 2016

Cell Physiol Biochem

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“…Inactivation of the VHL gene due to mutation or hypermethylation is the most frequently described genetic alteration in ccRCC. According to some reports the prevalence may reach as much as 60–80% [ 45 – 47 ]. Induction of IGFBP-3 through HIF-1α-mediated mRNA transcription has been described by Natsuizaka et al .…”

Section: Discussionmentioning

confidence: 99%

Expression of insulin-like growth factor family genes in clear cell renal cell carcinoma

Braczkowski¹,

Białożyt²,

Plato³

et al. 2016

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Aim of the studyDespite significant progress in the pathology of clear cell renal cell carcinoma (ccRCC), diagnostic and predictive factors of major importance have not been discovered. Some hopes are associated with insulin-like growth factors. The aim of the study was to compare the expression of genes for insulin-like growth factor family in tumours and in tissue of kidneys without cancer.Material and methodsFifty-two patients years with clear cell renal cell cancer were qualified to the study group; patients nephrectomised because of hydronephrosis were included in the control group. Expression of genes were evaluated by RT-PCR.ResultsExpression of IGFR-1 gene in tumour accounts for about 60% of cases. The incidence is higher than in corresponding adjacent non-cancerous kidney tissues and higher (but with no statistical significance) than in kidney without cancer.Expression of IGFR-2 gene in tumours has not been established. The incidence of the expression in corresponding adjacent non-cancerous kidney tissues is small. Expression of this gene has been present in all specimens from kidneys without cancer.Expression of IGFBP-3 gene ascertained in all (except four) cases of ccRCC and in the majority of clippings from adjacent tissue. It was not found in kidneys from the control group.IGF-1, IGF-2, and IGFR-1 mRNA copy numbers in ccRCC were higher than in the material from the control group

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“…Since Neumann et al reported that RCCs developing in patients with VHL disease had a better prognosis than sporadic RCCs [ 18 ], a series of studies investigated the correlation of somatic VHL alteration with pathological characteristics or prognosis in ccRCCs [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Some studies found that VHL alteration correlated with favorable pathological features or prognosis [ 22 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Salinas-Sánchez et al reported that VHL methylation was associated with worse survival [ 31 ]. Other studies failed to demonstrate the pathological or prognostic significance of VHL alteration in patients with ccRCC [ 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

Kim

Jang

et al. 2018

IJMS

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The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration (mutation, loss of heterozygosity, or promoter hypermethylation). However, the pathological or prognostic significance of VHL gene alteration has not been well defined. We conducted this meta-analysis to evaluate the association between VHL alteration and clinopathologic findings in ccRCCs. We performed a systematic computerized search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar (up to July 2018). From ten studies, 1,082 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for pathological features (nuclear grade and disease stage) or hazard ratios (HRs) with 95% CIs for overall survival (OS). VHL alteration was not significantly associated with nuclear grade (OR = 0.79, 95% CI: 0.59–1.06, p = 0.12) or disease stage (OR = 1.07, 95% CI: 0.79–1.46, p = 0.65). There was also no significant correlation between VHL alteration and OS (HR = 0.75, 95% CI: 0.43–1.29, p = 0.30). When we pooled HRs for OS according to the VHL alteration types, the combined HRs were 0.72 (95% CI: 0.47–1.11, p = 0.14) for VHL mutations and 1.32 (95% CI: 0.70–2.47, p = 0.39) for methylation. In conclusion, this meta-analysis indicates that VHL gene alteration is not significantly associated with the pathological features and survival in patients with ccRCC.

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Unique molecular alteration patterns in von Hippel-Lindau (VHL) gene in a cohort of sporadic renal cell carcinoma patients from Pakistan

Cited by 6 publications

References 21 publications

The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis

The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis

Expression of insulin-like growth factor family genes in clear cell renal cell carcinoma

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

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