Similar to the genomic CNVs in other cancers, the pathogenesis in VHL/PBRM1-negative ccRCC seems to be shaped by the accumulation of amplification in driver genes (IGFBP4, ERBB2, ERBB3, FGFR4, CDK2, and FLT4), the loss of function in tumor suppressor genes (Chmp1A, CADM2) and autophagy genes (PRAP1, ULK1). This evidence concerns the gene IGFBP4 and nonpapillary renal cell carcinoma.