Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon

Jean Pierre J. Issa, Yvonne L. Ottaviano, Paul Celano, Stanley R. Hamilton, Nancy E. Davidson, Stephen B. Baylin

Research output: Contribution to journalArticle

Abstract

We report that CpG island methylation, an epigenetic modification of DNA known to correlate closely with silencing of gene transcription, appears in the oestrogen receptor (ER) gene in a subpopulation of cells which increases as a direct function of age in human colonic mucosa. This same methylation change characterizes virtually all cells in all 45 colorectal tumours examined, including the earliest stages of tumour formation. ER gene expression is diminished or absent in colorectal tumours, and introduction of an exogenous ER gene in cultured colon carcinoma cells resulted in marked growth suppression. Our data suggest that methylation associated inactivation of the ER gene in ageing colorectal mucosa could be one of the earliest events that predispose to sporadic colorectal tumorigenesis.

Original languageEnglish (US)
Pages (from-to)536-540
Number of pages5
JournalNature genetics
Volume7
Issue number4
DOIs
StatePublished - Aug 1994

ASJC Scopus subject areas

  • Genetics

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