Background: Whole exome sequencing (WES) is increasingly used to identify genetic alterations of renal cell carcinoma (RCC). However, in Thailand, there is no report that clarifies the common somatic mutations and tumor mutational burden (TMB) in RCC. Therefore, the understanding of the tumor somatic mutational landscape could improve RCC management in the authors’ country.

Objective: To perform a descriptive study to identify common somatic mutated genes and TMB in clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and clear cell papillary renal cell carcinoma (ccpRCC).

Materials and Methods: The authors enrolled 13 patients, which consisted of 10 cases of ccRCC, two cases of pRCC, and one case of ccpRCC. DNA was isolated from peripheral blood mononuclear cells and tumor tissues for WES to identify tumor somatic mutations. The results were analyzed for correlations with tumor-aggressive features and compared with the public database.

Results: The authors identified common somatic mutations in VHL, SVIL, MUC16, CSMD3, CSMD1, and BAP1 in the study patients. In ccRCC cases, VHL mutation was detected in 90% of the cases corresponding to its high frequency in the TCGA’s ccRCC database. In pRCC cases, KDM6A was the only common mutated gene that overlapped with the top-ten most common genes in the TCGA’s pRCC database. Somatic mutations in BAP1, SETD2, and PBRM1 were significantly associated with tumor-aggressive features in the present study. The mean TMB of ccRCC, pRCC, and ccpRCC were 2.017, 2.143, and 6.61 mutations per megabase, respectively.

Conclusion: Identification of common somatic mutations and TMB in all subtypes of RCC from the present study showed the diversity of genetic alterations between Thai patients and the public database. This leads to specific therapeutic approaches for Thai patients. Moreover, the authors also detected similar associations between significant mutations reported in prior studies with the tumor-aggressive features in the present cases.

Keywords: Renal cell carcinoma; Somatic mutation; Tumor mutational burden; Whole exome sequencing

DOI: 10.35755/jmedassocthai.2024.3.13956

Received 19 December 2022 | Revised 22 February 2024 | Accepted 27 February 2024