Reduced Genomic 5-Methylcytosine Content in Human Colonic Neoplasia

Andrew P. Feinberg, Charles W. Gehrke, Kenneth C. Kuo, Melanie Ehrlich

Research output: Contribution to journalArticle

Abstract

DNA methylation appears to play an important role in both physiological and experimentally modified gene expression, and alterations in DNA methylation have been described in animal tumor models and in transformed cells and tumor cell lines. However, there have been comparatively few reports on DNA methylation in primary human malignancies, and these reports are somewhat contradictory. While individual genes have shown hypomethylation in colon cancer and premalignant adenomas as well as in lung cancer, other genes have shown increased methylation, and absolute measures of 5-methylcytosine content have shown decreases in malignancies but not in premalignant adenomas. We have used a sensitive quantitative measurement of 5-methylcytosine content by high performance liquid chromatography revealing an unequivocal hypomethylation of tumor DNA. An average of 8 and 10% reduction in genomic 5-methylcytosine content was seen in apparently all colon adenomas and adenocarcinomas, respectively, and there was no significant difference between benign and malignant tumors. This is a substantial quantitative alteration and suggests a pervasive abnormality in the control of DNA methylation. Surprisingly, three patients with the highest 5-methylcytosine content in their normal colon appear to have a germline predisposition to cancer (Lynch syndrome).

Original languageEnglish (US)
Pages (from-to)1159-1161
Number of pages3
JournalCancer Research
Volume48
Issue number5
StatePublished - Mar 1988
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Feinberg, A. P., Gehrke, C. W., Kuo, K. C., & Ehrlich, M. (1988). Reduced Genomic 5-Methylcytosine Content in Human Colonic Neoplasia. Cancer Research, 48(5), 1159-1161.