VHL (von Hippel-Lindau tumor suppressor)

Targeting PEA15 using ASOs offers a promising therapeutic strategy for HCC, particularly in the MES subtype. These findings provide a basis for further exploration of PEA15-targeted therapies to improve HCC outcomes.

Our case highlights the possibility of VHL-associated NET development in uncommon locations. Further studies are required to elucidate the correlation between VHL mutation sites and the clinical manifestation of the disease.

Conversely, use of an ASNS inhibitor significantly restrained the growth and metastasis of RCC cells in vitro and in vivo. In summary, our findings highlighted the critical role of L-Asn in RCC and identified ASNS as a novel substrate for VHL-mediated ubiquitination, presenting a potential new target for RCC treatment.

Genetic testing identified a pathogenic VHL mutation: NM_000551.4(VHL):c.508G>A, consistent with VHL type 2C phenotype. Systematic screening for other VHL-associated lesions was negative. This case highlights the diagnostic challenge posed by clinically silent pheochromocytomas and underscores the importance of genetic evaluation in atypical adrenal tumors.

Variants were significantly enriched in genes associated with GABAergic and serotonergic neuronal cell types, as well as in pathways regulating cell cycle and neurogenesis. These findings suggest that, in addition to VHL loss, dysregulation of neuronal differentiation programs and cell cycle control may play important roles in hemangioblastoma tumorigenesis.

Branched-chain amino acid metabolism and IL4I1 are pivotal in the progression of ccRCC. AS classification and the AIS score present a robust framework for personalized treatment strategies, while IL4I1 shows potential as a novel therapeutic target to enhance treatment efficacy.

While CCPCE can be morphologically indistinguishable from CCPRCT and share PAX8+/KRT7+/CAIX+ immunoreactivity, typically negative staining for RCC/GATA3 coupled with the generally low stage and good outcome for CCPRCT may favor CCPCE in challenging scenarios. Except for VHL mutations in a syndromic setting, CCPCE lacks other molecular alterations of CCRCC (e.g., SETD2, PBRM1, BAP1), although further confirmatory studies are needed.

In our study, the PR-619 inhibitor caused a decrease in the HIF2α protein level in 786-O, OS-RC-2, and SW839 cells, and MG132 treatment increased HIF2α protein expression after PR-619 treatment...We also confirmed that USP10 expression was upregulated in kidney cancer and had a positive correlation with HIF2α expression in RCC patient samples. Our results suggest that USP10 promotes HIF2α stability.

This study demonstrated that strict morphologic and immunohistochemical criteria can distinguish most CCRCCs mimicking CCPRCT from CCPRCT. The diagnosis of CCPRCT should be expanded to include tumors with monoallelic VHL alteration exhibiting typical morphologic and immunohistochemical features.

US Food and Drug Administration-approved DNMT inhibitors, such as decitabine and azacitidine, and investigational agents including RX-3117 and SGI-1027 selectively suppressed the growth of VHL-deficient RCC cells. Further mechanistic analysis showed that KCNK3 reactivation triggers TNF-α, MAPK and apoptotic signaling pathways, contributing to the observed synthetic lethality. Collectively, these findings establish DNMT inhibition as a synthetic lethal strategy in VHL-deficient RCC and highlight a potential therapeutic vulnerability for personalized treatment approaches.

No statistically significant differences in driver mutation prevalence or prognosis were observed between sarcomatoid and rhabdoid differentiation. These findings highlight the value of molecular stratification in elucidating pathogenesis and guiding targeted therapy for this aggressive ccRCC subtype, particularly emphasizing TP53 as a prognostic biomarker and TSC/MTOR alterations as potential therapeutic targets.

P1, N=40, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision and not related to safety concerns