It exhibits a different molecular signature than clear-cell carcinoma and is typically not associated with mutations in the VHL (von Hippel-Lindau) tumor suppressor gene. pRCC is less responsive to modern drugs introduced in the management of kidney cancer in the past decade.
Additional molecular genetic testing revealed somatic mutations and epigenetic events in genes typically associated with these specific histologic tumor types: oncocytoma harbored a second FLCN mutation (intron 12, IVS12+4 C>T), oncocytic papillary carcinoma harbored promoter methylation of FLCN, and a missense mutation in the MET gene (P246L), whereas clear cell carcinoma harbored inactivating VHL mutation (5-base pair deletion in exon 2) and VHL gene promoter methylation.
The percentage of vhl gene mutations in sporadic renal cell carcinoma was relatively low, mutations were seen more often in clear cell carcinoma and were not related to the classic clinical prognostic factors.
The relationship between the VHL gene and clear cell carcinoma, MET and papillary carcinoma, and the families of genes that they regulate, continues to be unraveled.