The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies

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.