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

Clear cell renal cell carcinoma (ccRCC) arising in the setting of von Hippel-Lindau (VHL) disease is a rare type of kidney cancer and features VHL germline mutation. This type of ccRCC is rarely characterised at the single-cell level. In this work, whole-exome sequencing and single-cell RNA sequencing (scRNA-seq) were conducted on one ccRCC sample with VHL disease. Integrating scRNA-seq and whole-exome sequencing data by the Seurat package, we determined the relationship between single-cell transcriptome features and gene mutations. Immunohistochemistry and immunofluorescence were performed on one VHL germline mutation ccRCC and six non-VHL germline mutation ccRCC samples. We revealed the gene expression characteristics of ccRCC with VHL germline mutation. The frameshift mutations in OBP2A and BCR1, and the elevated expression of COX7A1 were most specific characteristics of ccRCC tumor cells with VHL mutation. And the extensive infiltration of exhausted T cells was the characteristic of tumor microenvironment. In addition, we discovered the relationship between genetic mutations and immune checkpoints. This work highlights the single-cell transcriptome and DNA-level information of this rare ccRCC and will provide more genetic insights and references into this rare disease.