TY - JOUR
T1 - The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies
AU - de Joode, K.
AU - van de Geer, W. S.
AU - van Leenders, G. J. L. H.
AU - Hamberg, P.
AU - Westgeest, H. M.
AU - Beeker, A.
AU - Oosting, S. F.
AU - van Rooijen, J. M.
AU - Beerepoot, L. V.
AU - Labots, M.
AU - Mathijssen, R. H. J.
AU - Lolkema, M. P.
AU - Cuppen, E.
AU - Sleijfer, S.
AU - van de Werken, H. J. G.
AU - van der Veldt, A. A. M.
N1 - Funding Information: This study has been supported by the Erasmus Trustfonds and the Erasmus Foundation. Funding Information: This publication and the underlying study have been made possible partly based on the data that Hartwig Medical Foundation and the Center of Personalized Cancer Treatment (CPCT) have made available for the study. This study has been made available by the Erasmus Trustfonds and the Erasmus Foundation. Furthermore, we would like to thank the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA) for their assistance in retrieving and storing the pathological records of the included patients with RCC. Figure 1 was created with BioRender (https://biorender.com/). Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85163858205&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-023-37764-z
DO - https://doi.org/10.1038/s41598-023-37764-z
M3 - Article
C2 - 37400554
SN - 2045-2322
VL - 13
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 10720
ER -