METHYLATION OF THE ESTROGEN-RECEPTOR CPG ISLAND LINKS AGING AND NEOPLASIA IN HUMAN COLON

We report that CpG island methylation, an epigenetic modification of D NA known to correlate closely with silencing of gene transcription, ap pears in the oestrogen receptor (ER) gene in a subpopulation of cells which increases as a direct function of age in human colonic mucosa. T his same methylation change characterizes virtually all cells in art 4 5 colorectal tumours examined, including the earliest stages of tumour formation. ER gene expression is diminished or absent in colorectal t umours, and introduction of an exogenous ER gene in cultured colon car cinoma cells resulted in marked growth suppression. Our data suggest t hat methylation associated inactivation of the ER gene in ageing cotor ectal mucosa could be one of the earliest events that predispose to sp oradic cotorectal tumorigenesis.