RB1 and neoplasm: Furthermore, gene inactivation through hypermethylation of the CpG islands in the promoter region has been identified for many tumor suppressor genes, including the retinoblastoma tumor-suppressor gene (Rb), the von Hippel-Lindau tumor-suppressor gene (VHL), p16INK4a, the breast-cancer susceptibility gene 1 (BRCA1), and the MutL homolog 1 gene (hMLH1) [4,28,40–43].