Genomic characterization of clear cell renal cell carcinoma using targeted gene sequencing

Kidney cancer is one of the most lethal cancer types worldwide. The most common subtype of kidney cancer is clear cell renal cell carcinoma (ccRCC), and the somatic mutations of ccRCC have been identified through the development of large databases. The present study aimed to validate the status of the associated gene mutations in a Taiwanese cohort. Targeted sequencing was used to validate the mutation status of genes related to ccRCC in Taiwanese patients who had nephrectomy for kidney cancer. The top eight mutated genes in the Catalogue Of Somatic Mutations In Cancer (COSMIC) were selected. These genes were VHL, protein polybromo-1 (PBRM1), histone-lysine N-methyltransferase SETD2, BRCA1-associated protein-1 (BAP1), lysine-specific demethylase 5C (KDM5C), TP53, MTOR and PTEN. The association between the gene mutation status of VHL, PBRM1, SETD2 and BAP1 was validated with clinicopathological parameters as well as overall survival time. Tumor cells from 96 patients with ccRCC were target sequenced. The order of mutation rate of the eight aforementioned genes was similar to that reported within COSMIC. The present Taiwanese cohort exhibited lower PBRM1 and BAP1 mutation rates compared with average, with increased mutation rates for SETD2 and KDM5C. BAP1 mutation was associated with the tumor and cancerous stage. None of these four genes were positively associated with the overall survival of patients. The PBRM1 and SETD2 mutations were mutually exclusive to BAP1 mutation. Overall, the present study provided data confirming gene alteration in Taiwanese patients with ccRCC and showed some differences when compared with Western countries. Further comprehensive genomic and epigenomic studies, as well as downstream validation, are necessary to evaluate the impact of these differences.