Table 3.
Treatment, response, and VHL mutation status of the patients treated with anti-angiogenic therapies
| 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 |
PD progressive disease, SD Stable disease, RD Regressive disease, LOF loss-of-function, fs frameshift
aone patient with two mutations