5' CpG Island méthylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers

Loss of heterozygosity on chromosome 9p21 is one of the most frequent genetic alterations identified in human cancer. The rate of point mutations of pi6, a candidate suppressor gene of this area, is low in most primary tumours with allelic loss of 9p21. Monosomie cell lines with structurally unaltered pi6 show méthylation of the S' CpG island of pi6. This distinct méthylation pattern was associated with a complete transcriptional block that was reversible upon treatment with 5-deoxyazacytidine. Moreover, de novo méthylation of the 5' CpG island of pi6 was also found in approximately 20% of different primary neoplasms, but not in normal tissues, potentially representing a common pathway of tumour suppressor gene inactivation in human cancers.