Second, during tumor evolution, the infiltration of cytotoxic lymphocytes eliminates tumor clones with high immunogenicity, causing a selection of clones with reduced MHC expression that may present structural alteration, or “Hard” lesions, in the MHC loci or other genomic regions (e.g., B2M, IFN, STAT) distinct from the derived clone [61]. This evidence concerns the gene HLA-C and neoplasm.