VHL mutation

#TumorBoardTuesday 🤔What percentage of patients with RCC are germline VHL mutation carriers❓ (@MPishvaian)

For clarification- the 49% ORR is for patients w germline VHL mutation w a primary RCC of < 3 cm (@ClarkHenegan)

Agree! Approximately 70-80% of patients with renal cell carcinoma (RCC) have been found to be germline von Hippel-Lindau (VHL) mutation carriers. The VHL gene mutation is a well-known genetic alteration associated with the development of RCC. It is important to note that this… https://t.co/PbUjLe8hz2 (@nataliagandur)

I guess we would see studies in first line. However Belzutifan is an option for VHL gene mutated RCC (@DrVijayPatil11)

Belzutifan has been approved for patients with inherited VHL mutations (Von-Hippel Lindau syndrome). Looking forward to your groundbreaking research revealing somatic biomarkers for ccRCC patients! (@MarilenaMelas)

💥Can genomic characterization of RCC guide the decision for adjuvant treatment? 🔹943 ccRCC patients, 12 somatic gene analysis ☑️As the number of co-mutations accompanying the VHL gene increases, DFS significantly decreases. @CCR_AACR @OncoAlert https://t.co/BWz9qijoRn (@dr_yakupergun)

Most patients with clear cell #kidneycancer have VHL mutation in their cancer but not their normal cells. VHL syndrome is when *all* the cells in your body have VHL mutation and you develop #kidneycancer and other complications.This is where belzutifan is currently approved for. (@PavlosMsaouel)

Agree with Dr. @enarner : https://t.co/16rRpv0I6J is an exciting and fun paper to read, and even more fun to dissect for a N&V. Why does #VHL mutation cause #kidneycancer? Now we have a good idea why...#PAX8. Kudos to @SVanharanta and colleagues. (@KimrynRathmell)

VHL Mutation Analysis in Bilateral Clear Cell RCC Distinguishes Between Independent Primary Tumors and Contralateral Metastatic Disease | comment: Jun Gong MD @jgong15 https://t.co/e7n5a41xkb via @practiceupdate Rsrch from @AdamRMetwalli @markballmd and others frm @NCICCR_UroOnc (@gottsled)

Important paper from the @kaelin_lab Sensitivity of VHL mutant kidney cancers to HIF2 inhibitors does not require an intact p53 pathway https://t.co/MovygvuBCc (@FrezzaLab)

8/ From my post-doctoral work in the @kaelin_lab I knew that #VHL mutations are specific to ccRCC. We hypothesized PBRM1’s specificity as a predictive biomarker of ICB response was d/t interaction with VHL inactivation and HIF upregulation. (@WilliamKimMD)

Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease Great story - precision medicine that does not target the mutation (VHL) but rather is downstream consequences (HIF-2alpha) https://t.co/8j1Qsc1oKI (@Rfonsi1)

Everyone has two copies of each gene. For the VHL gene to stop working both copies need to be mutated. In VHL syndrome, one copy is mutated at birth in all cells in the body & the 2nd copy only in the #kidneycancer. In non-VHL syndrome, both copies are mutated only in the cancer. (@PavlosMsaouel)

I may have just answered my own question from a 2008 article “papillary or chromophobe type RCC which are not associated with VHL mutations.” Would that suggest this therapy may not be beneficial for noncc? (@kaydaustin)

Culminating a 20 year journey at @UTSWNews HIF2a gene discovery > atomic structure > vulnerability > lead compound > Peloton founding > phase I trial > identification of resistance mutations. A historical day for #VHL and soon all #RCC. https://t.co/HppzWwS1L6 (@JBrugarolas)

Please join us for the upcoming @df_hcc Kidney Cancer Program – @theNCI Joint Symposium “Bench to Bedside in VHL-Mutated Malignancies” https://t.co/I6gKQ0aI0c Date: Thursday, June 17th, 4:00pm – 7:00pm EST Questions? Contact Lindsey Bauer: lbauer@bidmc.harvard.edu (@DrChoueiri)

Day 9 #RCCAwareness In 2010: the first commonly mutated genes beyond VHL. SETD2 a histone methyltransferase for H3K36 and KDM5C and KDM6A, lysine demethylases for H3K4 and H3K27 respectively. Histone H3 regulation via methylation was the "it" event in RCC https://t.co/kqcZL7NS1Y (@KimrynRathmell)

Agreed completely. As a truncal mutation, VHL loss is not sufficient to transform RCC but the correction of VHL function would suffice to inhibit RCC tumor progression. Thanks for raising #RCCAwareness !! (@QingZhangLab)

Day 5 #RCCAwareness Building on the discovery of VHL mutation came the finding of a major transcription hub--disregulated Hypoxia Inducible Factors (HIF1 and HIF2) https://t.co/cGOOmFBzfQ driving VEGF and GLUT1 expression in #RCC without hypoxia. #Pseudohypoxia (@KimrynRathmell)

HIF2a inhibition in VHL mutant Kidney Cancer. Second example of synthetic lethality in the clinic! Congrats to @kaelin_lab for the pioneering work (@SBLabUCSF)