High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer

Wafik S. El-Deiry, Barry D. Nelkin, Paul Celano, Ray Whay Chiu Yen, Joseph P. Falco, Stanley R. Hamilton, Stephen B. Baylin

Research output: Contribution to journalArticle

Abstract

DNA methylation abnormalities occur consistently in human neoplasia including widespread hypomethylation and more recently recognized local increases in DNA methylation that hold potential for gene inactivation events. To study this imbalance further, we have cloned and localized to chromosome 19 a portion of the human DNA methyltransferase gene that codes for the enzyme catalyzing DNA methylation. Expression of this gene is low in normal human cells, significantly increased (30- to 50-fold by PCR analysis) in virally transformed cells, and strikingly elevated in human cancer cells (several hundredfold). In comparison to colon mucosa from patients without neoplasia, median levels of DNA methyltransferase transcripts are 15-fold increased in histologically normal mucosa from patients with cancers or the benign polyps that can precede cancers, 60-fold increased in the premalignant polyps, and >200-fold increased in the cancers. Thus, increases hi DNA methyltransferase gene expression precede development of colonic neoplasia and continue during progression of colonic neoplasms. These increases may play a role in the genetic instability of cancer and mark early events in cell transformation.

Original languageEnglish (US)
Pages (from-to)3470-3474
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number8
DOIs
StatePublished - 1991

ASJC Scopus subject areas

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