Potential Role of VHL, PTEN, and BAP1 Mutations in Renal Tumors

Abstract

The genetic profiling of renal tumors has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. The VHL, PTEN, and BAP1 genes are often mutated in renal tumors. The frequency and clinical relevance of these mutations in renal tumors are still being researched. In our study, we investigated VHL, PTEN, and BAP1 genes and the sequencing of 24 samples of patients with renal tumors, revealing that VHL was mutated at a noticeable frequency (25%). Six of the investigated samples showed mutations, and one genetic polymorphism (rs779805) was detected in both heterozygote and homozygote forms. PTEN gene mutation was observed in only one sample, and one specimen showed genetic polymorphism. In the case of the BAP1 gene, all of the samples were wild types. Interestingly, VHL mutation was detected in two female patients diagnosed with AML and in one with oncocytoma. We assume that VHL or PTEN mutations may contribute to the development of human renal cancer. However, the overall mutation rate was low in all specimens investigated, and the development and prognosis of the disease were not exclusively associated with these types of genetic alterations.

Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival

“…Apart from VHL gene inactivation, other epigenetic genes also play a contributing role in ccRCC development, which mainly includes phosphatase and tensin homolog (PTEN) and breast cancer type-1 (BRCA-1)associated protein-1 (BAP1) [23]. The latest study by Szegedi et al confirmed that VHL or PTEN mutations may contribute to the development of human renal cancers [27].…”

YAP represses the TEAD–NF-κB complex and inhibits the growth of clear cell renal cell carcinoma

“…Clear cell renal cell carcinoma (ccRCC) accounts for 75% of all kidney cancer cases ( 3 ). Most patients with ccRCC harbor von Hippel–Lindau ( VHL ) gene abnormalities ( 4 ). The encoded VHL protein is an E3 ubiquitin ligase that targets hypoxia-inducible factors (HIFs) for degradation; the inactivation of VHL and the consequent dysregulation of HIF pathway signaling are major drivers of ccRCC growth and progression ( 5 , 6 ).…”