Research Papers:

Prevalence and clinical significance of VHL mutations and 3p25 deletions in renal tumor subtypes

Franziska Büscheck, Christoph Fraune, Ronald Simon _, Martina Kluth, Claudia Hube-Magg, Christina Möller-Koop, Imren Sarper, Kathrin Ketterer, Tjark Henke, Christian Eichelberg, Roland Dahlem, Waldemar Wilczak, Guido Sauter, Margit Fisch, Till Eichenauer and Michael Rink

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Oncotarget. 2020; 11:237-249. https://doi.org/10.18632/oncotarget.27428

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Franziska Büscheck1, Christoph Fraune1, Ronald Simon1, Martina Kluth1, Claudia Hube-Magg1, Christina Möller-Koop1, Imren Sarper1, Kathrin Ketterer1, Tjark Henke1, Christian Eichelberg3, Roland Dahlem2, Waldemar Wilczak1, Guido Sauter1, Margit Fisch2, Till Eichenauer2 and Michael Rink2

1 Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2 Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

3 Urologische Praxis Straubing, Straubing, Germany

Correspondence to:

Ronald Simon,email: [email protected]

Keywords: renal cell tumors; von Hippel-Lindau gene; VHL mutation; 3p copy number; fluorescence in-situ hybridization

Received: August 14, 2019     Accepted: December 29, 2019     Published: January 21, 2020


Purpose: To evaluate prevalence and clinical impact of VHL mutations and deletions (3p), a cohort of consecutive kidney tumors was analyzed by DNA sequencing and fluorescence in-situ hybridization (FISH).

Patients and Methods: The study includes 1,805 patients with renal tumors who were surgically treated at the Department of Urology at the University Medical Center Hamburg-Eppendorf between 1994 and 2015. The cohort included 1,176 clear cell, 270 papillary, 101 chromophobe, and 28 clear cell (tubulo) papillary cancers, as well as 149 oncocytomas and 81 less common subtypes.

Results: Among 431 successfully analyzed tumors, VHL mutations were found in 59.3% of clear cell, 5.2% of papillary, 3.1% of chromophobe carcinomas and in 7.3% of oncocytomas as well as in the rare kidney tumor types (25%–60%). FISH analysis was successful in 1,403 cases. 3p25 deletion was found in 57.2% of clear cell, 17.6% of papillary, 17.7% of chromophobe carcinomas and in 11.9% of oncocytomas as well as in the rare kidney tumor types (16.7%–50%). No statistically significant associations between VHL mutation/deletion and tumor grade, stage, and clinical outcome was found. Only in the subgroup of papillary cancers, 3p deletion was significantly associated with lymph node and distant metastasis as well as with poor patient outcome (p < 0.05 each).

Conclusions: The presence of a VHL mutation in virtually all renal tumor subtypes suggests that VHL analysis cannot be used to distinguish between renal tumor subtypes. Consequently, anti-VHL treatment strategies should not be limited to patients with clear cell cancer.

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