Abstract
The genomic landscape of advanced renal cell cancer (RCC) was characterized for 91 patients to identify actionable targets and signatures by combining whole-genome sequencing (WGS) with matched RNA sequencing (RNA-Seq). WGS data were analyzed for somatic small variants, copy-number alterations (CNAs) and structural variants. Somatic aberrations were analyzed for driver genes, CNA drivers, mutational signatures, catastrophic events and fusion genes. For papillary and clear cell RCC, potential actionable drug targets were detected by WGS in 89% and 100% of the patients, respectively. RNA-Seq data of clear cell and papillary RCC were clustered according to a previously developed angio-immunogenic gene signature. 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 date. Prospective clinical trials are needed to evaluate the impact of genomic and transcriptomic diagnostics on survival outcome for advanced RCC patients.
Competing Interest Statement
P.H. declares consultancy roles for Astellas, MSD, Ipsen, Pfizer, AstraZeneca, and Bristol-Myers Squibb, all outside the submitted work; H.M.W. declares honoraria from Roche and Astellas and travel expenses from Ipsen and Astellas, all outside the submitted work; S.F.O declares research grants from Novartis, Pfizer and Celldex Therapeutics and advisory board for Bristol Myers Squibb (all paid to the institution); M.L. declares speakers fee of BMS and advisory board of MSD, both paid to institution; R.H.J.M. declares speakers fee from Novartis and advisory role for Servier, patency from Pamgene, and investigator-initiated research (paid to institution) from Astellas, Bayer, Boehringer-Ingelheim, Cristal Therapeutics, Pamgene, Pfizer, Novartis, Roche, Sanofi, Servier, all outside the submitted work; M.P.L. declares advisory board for Amgen, Astellas, Astra Zeneca, Bayer, INCa, Janssen Cilag BV, MSD, Novartis, Pfizer, Roche, Sanofi, Servier, consulting role for Julius Clinical and Research Grants (paid to institution) from Astellas, Janssen, MSD, Sanofi, all outside the submitted work; H.J.G.W. declares speakers honoraria from Bayer, Depositary receipts for shares from Cergentis B.V. all outside the submitted work; A.A.M.V. reports advisory board (all paid to institution) of BMS, MSD, Merck, Pfizer, Ipsen, Eisai, Pierre Fabre, Roche, Novartis, Sanofi, all outside the submitted work. All other authors declare no competing interests.
