Investigation of tumor heterogeneity using single cell transcriptomics in Von Hippel-Lindau related renal cancer

Von Hippel-Lindau (VHL) dìsease is a rare inherited disorder caused by the loss of the VHL gene and characterized by benign and malignant tumors in several organs. Patients with VHL disease have risk of developing multiple primary clear cell renal carcinomas (ccRCC). Patients are managed with multiple sessions of renal surgery causing renal failure and complication of dialysis or systemic progression and cancer-specific mortality. Our hypothesis states that multiple independent tumors from one VHL patient may display inter-tumoral heterogeneity characterized by differences in tumor grade, metabolic, stromal, and immune cell features that may cause different response to systemic therapy. We took advantage of a nephrectomy from one VHL patient to investigate molecular and microenvironmental factors in five independent primary tumors. Overall design: To assess the cellular and molecular landscape of multiple tumors within the index VHL patient, five independent tumors (i.e., L1, L2, L4, L5.1 and L7) and one sample of normal parenchyma (i.e. LN) were selected and processed with single-cell RNA sequencing (scRNAseq).