TP53 and neoplasm: It is widely accepted that gene promoters, especially key tumor suppressor genes, are unmethylated in normal tissues and highly methylated in cancer tissues.20 P16, a tumor suppressor encoded by CDKN2A, has been found to gain de novo methylation in ~20% of different primary neoplasms.21 Mutations in important and well-studied tumor-suppressive genes, such as P53 and BRCA1, are frequently identified in multiple cancers.22–24 Studies have found that the level of methylation is positively associated with tumor size.