Skip to main content

Table 3 Treatment, response, and VHL mutation status of the patients treated with anti-angiogenic therapies

From: Characterization of VHL missense mutations in sporadic clear cell renal cell carcinoma: hotspots, affected binding domains, functional impact on pVHL and therapeutic relevance

Mutation Mutation consequence Functionality prediction Interacting partners Disease progression status Treatment pT stage Fuhrman grade
c.163delG/p.Glu55ArgfsX11 fs LOF   PD Pazopanib > Everolimus 3 3
c172delC/p.Arg58GlyfsX9 fs LOF   PD IFNa > Pazopanib   
c.194C > T/p.Ser65Leu missense stabilizing HIF1αN/VDU1/USP33/VDU2/USP20/RPB7/VHLAK/BCL2L11/RPB1 PD Sunitinib   
c.240 T > A/p.Ser80Arg missense destabilizing HIF1αN/VDU1/USP33/VDU2/USP20/RPB7/VHLAK/BCL2L11/HIF1α/EPAS1/RPB1 PD IFNa > Sorafenib 1  
c. 262 T > A/p.Trp88Arg missense highly destabilizing HIF1αN/RPB7/VHLAK/BCL2L11/HIF1α/EPAS1/RPB1/PRKCZ PD Sunitinib 3 3
c.268_273del/p.Asn90_Phe91del in frame LOF   PD Sunitinib   3
c.IVS1 + 1G > A (c.340 + 1G > A) splice mut LOF   PD Sorafenib > Sunitinib > Everolimus   
c.345_364del/p.Leu116ArgfsX9 fs LOF   PD IFNa > Sorafenib   
c.349delT/p.Trp117GlyfsX42 fs LOF   PD Sunitinib 3 3
c.484 T > C/p.Cys162Arg missense neutral VHLAK/p53/Nur77/EloC/HuR PD Sunitinib > Sorafenib > Everolimus > Pazopanib 3 3
c.497_505del9/p.Arg167ValdelSerLeu in frame LOF   PD Sunitinib 3 3
C.580_583delinsAA/p.Val194LysfsX61 fs LOF   PD Sunitinib > Sorafenib   
c.586A > T/p.Lys196X nonsense LOF   PD Sunitinib > Sorafenib > Everolimus 1  
  wild-type wild-type   PD Pazopanib 3 4
  wild-type wild-type   PD Sunitinib > Pazopanib > Sorafenib > Everolimus 4 3
  wild-type wild-type   PD Sunitinib 2 3
c.161_162delTG/p.Met54ArgfsX77 fs LOF   SD Sunitinib 3 4
c.203C > A/p.Ser68X nonsense LOF   SD Sorafenib > Pazopanib > Everolimus 3 4
c.327insA/p.His110ProfsX22 fs LOF   SD Sunitinib > Sorafenib 1 4
c.IVS1 + 2 T > A (c.340 + 2 T > A) splice mut LOF   SD Pazopanib > Axitinib 3 3
c.345insC/p.Leu116ProfsX15 fs LOF   SD Bevacizumab > IFNa > Pazopanib 3 4
c.350delG/p.Trp117CysfsX42 fs LOF   SD IFNa/Bevacizumab 1 3
c.481C > T/p.Arg161X nonsense LOF   SD Sorafenib 2 2
  wild-type wild-type   SD Sunitinib > Sorafenib > Everolimus   
c.167_168delCC/p.Ala56GlyfsX75 fs LOF   RD Sorafenib 3 1
c.227_229del3/p.Phe76del in frame LOF   RD Pazopanib > Sunitinib 1 3
c.340G > T/p.Gly114Cys missense neutral HIF1αN/VHLAK/BCL2L11/HIF1α/EPAS1/RPB1/PRKCZ/CARD9/TUBA4A/KIF3A/SP1/JADE1/PRKCD/aPKC-λ/ι/EEF1A1 RD IFNa > Bevacizumab 2 3
c.383 T > C/p.Leu128Pro a missense higly destabilizing HIF1αN/VHLAK/BCL2L11/EEF1A1 RD Pazopanib 3 4
c.430G > T/p.Gly144X a nonsense LOF   RD Pazopanib 3 4
c.458 T > C/p.Leu153Pro missense destabilizing HIF1αN/VHLAK/PRKCD/CCT-ζ-2/TBP1 RD Sunitinib 2 3
  wild-type wild-type   RD Pazopanib > Everolimus 3 3
  1. PD progressive disease, SD Stable disease, RD Regressive disease, LOF loss-of-function, fs frameshift
  2. aone patient with two mutations