Molecular Pathogenesis of Renal Cell Carcinoma: A Review

Gomy, Israel; Silva, Wilson A.

doi:10.5772/27950

Cited by 3 publications

(4 citation statements)

References 54 publications

(59 reference statements)

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“… 14 None of the cases in present study showed exon 1 mutation. Single case of CCRCC that was negative for mutations in our study could be due to possibility of other gene mutations involved such as FH, SDH, PBRM 1, and BAP 1 as expressed by Gomey and Silva 15 and Pawloski et al 16 …”

Section: Discussionmentioning

confidence: 59%

“…Surprisingly 2 cases of papillary RCC in our series showed VHL mutations with two repeated PCR analysis of these two cases. This finding warrants further investigations to evaluate the possibility of co-existence of VHL with c-Met pathway Gomey and Silva 15 has also expressed that MET and VHL signaling pathways intersect via pVHL-mediated regulation of HIF function.…”

Section: Discussionmentioning

confidence: 79%

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Expression of Von Hippel – Lindau (Vhl) Gene Mutation in Diagnosed Cases of Renal Cell Carcinoma

et al. 2014

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Objective: To evaluate the expression of Von Hippel Lindau (VHL) gene in diagnosed cases of renal cell carcinoma. Methods: This cross sectional study was conducted in department of Pathology, Basic Medical Sciences Institute, JPMC, Karachi, from January 2007 to December 2012. Paraffin embedded blocks of 30 cases of radical nephrectomy specimens diagnosed as renal cell carcinoma including CCRCC 21 (70%) CCPRCC, 3 (10%), PRCC 2 (6.79%), hybrid tumor 4 (13.3%), chromophobe tumor (0%) processed for VHL gene expression on Polymerase Chain Reaction. Results: All the 30 cases previously diagnosed as renal cell carcinoma were processed on PCR, VHL gene mutations were seen in 20 (95.23%) of CCRCC while a single case was negative for VHL mutations. All CCPRCC were negative for VHL mutation. Among the hybrid tumor 03 cases with foci of clear cells show VHL mutation while a single case showing combination of clear cells and chromophobe cells was negative for mutation. Both the cases of PRCC were positive for mutation. Exon 3 mutation at base pair 194 seen in 8 (32%) cases and Exon 2 mutation at base pair 150-159 seen in 17 (68%) cases. None of the cases showed Exon 1 mutation. Conclusion: The present study shows that majority of CCRCC showed VHL mutation including the hybrid tumor with clear cell component in our population.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 79%

Expression of Von Hippel – Lindau (Vhl) Gene Mutation in Diagnosed Cases of Renal Cell Carcinoma

et al. 2014

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“…The FH gene encodes for a protein called fumarate hydrogenase, which catalyzes the formation of L-malate from fumarate in the Kreb’s cycle. FH inactivation leads to accumulation of intracellular fumarate, which in turn leads to succinate accumulation, with consequent VHL-independent stabilization of hypoxia-inducible factor 1-α subunit, causing upregulation of vascular endothelial growth factor (VEGF) and glucose transporter 1, contributing to carcinogenesis [18] . Upregulation of VEGF and glucose transporter 1 is known to underlie the molecular mechanism of high-grade RCC [19] .…”

Section: Discussionmentioning

confidence: 99%

Durable Response to Pazopanib in a Patient with Fumarate Hydratase-Mutant Tubulocystic Renal Cell Carcinoma

Othman¹,

Kumar

Qureshi

et al. 2023

Case Rep Oncol

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Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor and has been recently included as a distinct entity in WHO classification of renal neoplasms. We report the case of a patient with metastatic tubulocystic RCC whose disease progressed through standard of care treatment for nonclear RCC. However, genetic analysis revealed a germline pathogenic variant of fumarate hydratase (FH) gene, and the patient had a sustained and durable response to pazopanib.

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“…When FH malfunctions, the enzymatic activity of FH decreases, causing fumarate to accumulate. This, in turn, leads to succinate accumulation, stabilizing the hypoxia-inducible factor 1-alpha subunit, and causing the upregulation of vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT1), thereby contributing to the carcinogenesis of high-grade RCC [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling

Ueki

Sugano

Misu

et al. 2021

IJMS

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Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient’s family was advised to undergo genetic counseling to consider additional RCC screening.

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Molecular Pathogenesis of Renal Cell Carcinoma: A Review

Cited by 3 publications

References 54 publications

Expression of Von Hippel – Lindau (Vhl) Gene Mutation in Diagnosed Cases of Renal Cell Carcinoma

Expression of Von Hippel – Lindau (Vhl) Gene Mutation in Diagnosed Cases of Renal Cell Carcinoma

Durable Response to Pazopanib in a Patient with Fumarate Hydratase-Mutant Tubulocystic Renal Cell Carcinoma

Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling

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