Multifocal renal oncocytoma in a patient with Von Hippel-Lindau mutation

Fiske, Joshua; Patel, Rahila; Kau, Eric; Pappas, John; Garcı́a, Roberto; Taneja, Samir S.

doi:10.1016/j.urology.2005.06.122

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…Three of the patients identified with VHL mutations belonged to the ccRCC histotype, two were classified as angiomyolipomas, and one was described as oxyphilic adenoma. These results are in contrast with the earlier opinion that VHL mutations are exclusively restricted to ccRCC and similar to the results described in previous studies [43]. Teh et al reported a case of a patient with bilateral multiple oncocytomas and cysts associated with a constitutional translocation and a rare constitutional VHL missense substitution [48].…”

Section: Discussionsupporting

confidence: 87%

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

Szegedi

Szabó

Kállai

et al. 2023

JCM

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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.

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Section: Discussionsupporting

confidence: 87%

“…Genetic testing highlighted partial VHL gene deletion in a case study of a 63-year-old man with bilateral and multifocal renal oncocytoma. Partial VHL gene deletion suggests a higher risk of renal cell carcinoma than that seen in patients with complete deletions of the VHL gene [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

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

Szegedi

Szabó

Kállai

et al. 2023

JCM

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“…This analysis showed the presence of a left kidney oncocytoma, a very rare clinical manifestation associated with the disease (Fiske et al 2005;Teh et al 1998).…”

Section: Human Samples and Clinical Datamentioning

confidence: 83%

An 11-bp duplication in the promoter region of the VHL gene in a patient with cerebellar hemangioblastoma and renal oncocytoma

et al. 2007

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“…Very few cases of renal oncocytoma occurring in the context of a VHL syndrome have been described [11, 12], underlining the extremely low prevalence of this type of benign neoplasm when VHL is mutated. This is likely due to the fact that the functional trigger for tumorigenesis in the presence of VHL mutations is HIF1 α chronic stabilization, as loss of function mutations of the tumor suppressor lead to a lack of HIF1 α ubiquitination and subsequent proteasome-mediated degradation.…”

Section: Discussionmentioning

confidence: 99%

A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma

Luise

Guarnieri

Ceccarelli

et al. 2019

Oxidative Medicine and Cellular Longevity

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The Von Hippel-Lindau (VHL) syndrome has been rarely associated with renal oncocytomas, and tumors usually show HIF1α chronic stabilization. By contrast, oncocytomas mainly associated with respiratory chain (RC) defects due to severe mitochondrial DNA (mtDNA) mutations are incapable of stabilizing HIF1α, since oxygen consumption by the RC is dramatically diminished and prolylhydroxylase activity is increased by α-ketoglutarate accumulation following Krebs cycle slowdown. Here, we investigate the cooccurrence of a pseudohypoxic condition with oncocytic transformation in a case of VHL-associated renal oncocytoma. While HIF1α was abundant in nuclei concordantly with defects in VHL, negative staining of its targets carbonic anhydrase IX (CAIX) and glucose transporter GLUT1, usually overexpressed in VHL-associated neoplasms, suggested HIF1α to be present in its inactive (hydroxylated) form. MtDNA sequencing and immunohistochemistry analyses revealed a MT-CO1 stop-gain mutation and cytochrome c oxidase loss. We suggest that a mitochondrial respiration impairment may lead to hyperhydroxylation of the transcription factor, which we confirmed by specific staining of hydroxylated HIF1α. Such inactive form hence accumulated in the VHL-deficient tumor, where it may contribute to the benign nature of the neoplasm. We propose that the protumorigenic role of HIF1α in VHL cancers may be blunted through drugs inhibiting mitochondrial respiratory complexes, such as metformin.

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Multifocal renal oncocytoma in a patient with Von Hippel-Lindau mutation

Cited by 7 publications

References 6 publications

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

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

An 11-bp duplication in the promoter region of the VHL gene in a patient with cerebellar hemangioblastoma and renal oncocytoma

A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma

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