To provide a comprehensive overview of the functional role of 16q loss and IFNR in RCC progression, we designed gain-of-function studies in renal organoids and normal renal tubular cell lines established from a murine model of Down syndrome with a partial trisomy of chromosome 16 spanning the IFNR cluster (Ts65Dn)23. This evidence concerns the gene IFNAR2 and renal cell adenocarcinoma.