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Background  This study aimed to assess the feasibility of a pan-cancer panel assay for high-risk renal cell carcinoma (RCC) in the Korean population. We also analyzed the clinical and genetic factors contributing to metastasis in clear cell RCC.    Methods  Thirty-one patients with advanced RCC who underwent radical nephrectomy were analyzed. A 1.8 Mb multi-cancer panel (including 25 RCC-related genes, such as VHL, PBRM1, SETD2, and MET), comprising 181 target genes, 23 fusion genes, and 45 drug target lesions developed by Seoul National University Hospital, was used for this study.    Results  We extracted DNA from 30 of the 31 (96.7%) RCC specimens. Twenty-one patients (average age 63.3 ± 11.3 years) with clear cell RCC, 5 with papillary RCC, 3 with chromophobe RCC, and one patient, each with MiT family translocation carcinoma RCC and succinate dehydrogenase deficiency RCC, were analyzed. The sequencing depth was 430.8 ± 206.6 and 97 mutations (7.3 ± 2.7 mutations per patient) were detected. The most commonly mutated genes were  VHL  (46%),  PBRM1  (30%), and  BAP1 ,  NOTCH4 , and  POLQ  (23.33% each). Compared with TNM stage matched data from TCGA of clear cell RCC,  VHL  and  PBRM1  are most common in both cohorts. Univariate and multivariate analyses revealed that tumor size (Hazard ratio = 2.47,  p  = 0.04) and  PBRM1  (Hazard ratio = 28.69,  p  = 0.05) were related to metastasis in clear cell RCC.    Conclusion  The pan-cancer panel comprised of RCC-related genes is a feasible and promising tool to evaluate genetic alterations in advanced RCC. However, large-scale studies and a focus on the clinical utility of this cancer panels is needed.

Sharing the initial experience of pan-cancer panel analysis in high-risk renal cell carcinoma in the Korean population