Of note, analysis of TCGA showed that 11,2% of renal cell carcinoma (RCC) and ∼5% of pancreatic tumors have inactivating RAD18-deletions and 6,7% of malignant peripheral nerve sheath tumors lack RAD6B. As each TLS polymerase tolerates preferential types of lesions [14], DDT defects are predicted to render tumors hypersensitive to specific lesions that can be inflicted by many endogenous and exogenous DNA damaging agents, including clinically approved and widely applied DNA crosslinking anti-cancer drugs. Here, RAD18 is linked to hereditary clear cell renal cell carcinoma.