Comprehensive <scp>mRNA</scp> Expressional Analysis of <scp>SMARCB1</scp>‐Deficient Renal Cell Carcinoma in Patients Without Hemoglobinopathies

The molecular characteristics of switch/sucrose non-fermentable-related BAF chromatin remodeling complex subunit B1 (SMARCB1)-deficient renal cell carcinoma (RCC), particularly in patients without any hemoglobinopathies, remain unknown. Furthermore, the molecular similarities between SMARCB1-deficient RCC without hemoglobinopathies and renal medullary carcinoma (RMC), as well as malignant rhabdoid tumor of the kidney (MRTK), have not been clarified. In this study, we analyzed the mRNA and protein expressions of three SMARCB1-deficient RCCs without hemoglobinopathies using the nCounter Gene Expression Assay, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qPCR), and compared them with those of MRTKs. As results from nCounter, the mRNA expression patterns of SMARCB1-deficient RCC and MRTK differed completely from each other. We identified 93 genes, including BCL2, that were significantly upregulated in SMARCB1-deficient RCC. Enrichment analysis revealed that PI3K Akt signaling was an enriched term in SMARCB1-deficient RCC but not in MRTK. The immunohistochemical expressions of Bcl-2 in SMARCB1-deficient RCC and MRTK supported the nCounter results. Our data showed that SMARCB1-deficient RCC without hemoglobinopathies is a distinct entity from MRTK. We also discussed possible clinicopathological and molecular differences between SMARCB1-deficient RCC without hemoglobinopathies and RMC. The distinctions among these SMARCB1-deficient renal tumors identified in our study would significantly enhance diagnosis and develop new therapeutic strategies.