Integrating whole-exome sequencing and scRNA-seq reveal the characteristic of clear cell renal cell carcinoma arising in the setting of VHL disease

Clear cell renal cell carcinoma (ccRCC) arising in the setting of VHL disease is a rare type of kidney cancer. Occurring VHL germline mutation is the genetic feature of this disease. However, the characteristic of this special type of ccRCC at the single-cell level is still unknown. Here, we performed single-cell RNA sequencing (scRNA-seq) and whole-exome sequencing on a ccRCC sample with VHL disease. The relationship between single-cell transcriptome features and gene mutations was revealed. Two marker genes (CALD1 and COX7A1) for tumor cells were identified, which was validated by IHC experiments. We revealed the characteristics of immune microenvironment in ccRCC with VHL germline mutation at single-cell resolution, and discovered the relationship between genetic mutations and immune checkpoints. Collectively, this study highlighted the single-cell transcriptome and DNA-level information of the rare ccRCC arising in the setting of VHL disease, which could provide new insights into the diagnosis and treatment of ccRCC.