Differences in the clinical course and treatment responses in individual patients with advanced renal cell carcinoma (RCC) can largely be explained by the different genomics of this disease. To improve the personalized treatment strategy and survival outcomes for patients with advanced RCC, the genomic make-up in patients with advanced RCC was investigated to identify putative actionable variants and signatures. In this prospective multicenter study (NCT01855477), whole-genome sequencing (WGS) data of locally advanced and metastatic tissue biopsies and matched whole-blood samples were collected from 91 patients with histopathologically confirmed RCC. WGS data were analyzed for small somatic variants, copy-number alterations and structural variants. For a subgroup of patients, RNA sequencing (RNA-Seq) data could be analyzed. RNA-Seq data were clustered on immunogenic and angiogenic gene expression patterns according to a previously developed angio-immunogenic gene signature. In all patients with papillary and clear cell RCC, putative actionable drug targets were detected by WGS, of which 94% were on-label available. RNA-Seq data of clear cell and papillary RCC were clustered using a previously developed angio-immunogenic gene signature. Analyses of driver mutations and RNA-Seq data revealed clear differences among different RCC subtypes, showing the added value of WGS and RNA-Seq over clinicopathological data. By improving both histological subtyping and the selection of treatment according to actionable targets and immune signatures, WGS and RNA-Seq may improve therapeutic decision making for most patients with advanced RCC, including patients with non-clear cell RCC for whom no standard treatment is available to data. Prospective clinical trials are needed to evaluate the impact of genomic and transcriptomic diagnostics on survival outcome for advanced RCC patients.
Scientific reports. 2023 Jul 03*** epublish ***
K de Joode, W S van de Geer, G J L H van Leenders, P Hamberg, H M Westgeest, A Beeker, S F Oosting, J M van Rooijen, L V Beerepoot, M Labots, R H J Mathijssen, M P Lolkema, E Cuppen, S Sleijfer, H J G van de Werken, A A M van der Veldt
Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands., Department of Pathology, Erasmus MC, Rotterdam, The Netherlands., Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands., Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands., Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands., Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Department of Internal Medicine, Martini Hospital, Groningen, The Netherlands., Department of Internal Medicine, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands., Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands., Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands., Cancer Computational Biology Center, Erasmus MC Cancer Institute, University Medical Center, Internal Postal Address NA-1218, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. ., Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. .