VHL mutation

This integrative study identifies a six-gene signature, recurrent RNA editing-derived neoantigens, and miRNA networks in RCC. By connecting genomic, epigenetic, and immune features, it provides mechanistic insights into RCC progression and supports precision immuno-oncology and vaccine development.

Both in vitro and in vivo, the HIF-2α inhibitor belzutifan (PT2977) effectively suppressed this signaling axis and reversed the tumor-promoting effects caused by PARP1 overexpression. Collectively, our findings elucidate a critical role for the HIF-2α/TRIB3/PARP1 axis in ccRCC progression, revealing potential therapeutic targets and rational combination strategies for this disease.

Further genetic testing revealed that the patient was positive for a VHL mutation. There are only a few reports of intraventricular HBs that are found in the 4th ventricle in pediatric patients with less discussing solid HBs, so evaluation of this case can provide a valuable opportunity to compare and reflect on the nature of this rare presentation and contribute toward understanding the best approaches for treating these rare conditions.

The patient recovered uneventfully with favorable prognosis. This case contributes to the limited literature on ESC RCC in young female patients.

Parapapillary RH can masquerade as an epiretinal membrane over the optic disc, posing a diagnostic challenge. Histopathological confirmation and genetic evaluation are essential to establish the diagnosis and to identify underlying VHL disease.

The approach described herein may also serve as a blueprint for developing agents to correct destabilized mutations underlying other human diseases. Designed small molecules that re-fold and re-activate destabilized mutant VHL Lead agent re-folds and re-activates multiple common VHL mutants This approach may apply to other destabilized proteins that underlie human disease.

A review of all five previously reported BRCA2‑associated RCCs revealed that all six reported cases (including ours) shared certain features: mixed papillary and solid architecture, high‑grade cytology with prominent nucleoli, and absence of other RCC‑defining molecular drivers. Our case not only reinforces the previously reported features but also expands the morphological spectrum of BRCA2‑associated RCC, providing further evidence that this may represent a distinct subtype of RCC.

The association of BAP1 mutation in ccRCC with poor prognosis further supports its value in prognostications. Moreover, the model visualization reveals morphological signatures associated with gene mutations, offering preliminary insights into genotype-morphology relationships.

Moreover, combining cc-885 with an EPAS1 inhibitor, belzutifan, significantly enhanced the anti-tumor efficacy. Our findings provide a novel and precise therapeutic strategy for VHL-deficient ccRCC by targeting ETS1 degradation and disrupting the ETS1-EPAS1 complex.

To our knowledge, this report is the first to describe a molecularly profiled CCC with somatic VHL inactivation. These results expand the evolving genomic spectrum of CCC beyond its previously known IDH-wildtype status and suggest that VHL pathway dysregulation may contribute to tumorigenesis in a subset of cases.

The functional effects of HIF pathway inhibitors (GN44028, KC7F2, and FM19G11) and sunitinib were analysed in VHL-mutant 786-O and VHL-wild-type Caki-1 cell lines using SRB viability assay, cell cycle analysis, wound closure assay, and RT-qPCR of HIF-related genes, with comparison to non-malignant HK-2 cells...GN44028 did not demonstrate clear selectivity over non-malignant HK-2 cells. Overall, nuclear HIF activation is associated with aggressive ccRCC biology, and broader HIF pathway modulation warrants further experimental investigation; however, the clinical findings remain exploratory, and therapeutic selectivity and translational relevance are not yet established.

Germline testing revealed a VHL p.Asp126Asn mutation. This "dual-tracer" strategy provided complementary information on glucose metabolism and somatostatin receptor expression, facilitating prognostic stratification and therapeutic decision-making in VHL-mutated pheochromocytoma.