MGMT promoter methylation and field defect in sporadic colorectal cancer

Lanlan Shen, Yutaka Kondo, Gary Rosner, Lianchun Xiao, Natalie Supunpong Hernandez, Jill Vilaythong, P. Scott Houlihan, Robert S. Krouse, Anil R. Prasad, Janine G. Einspahr, Julie Buckmeier, David S. Alberts, Stanley R. Hamilton, Jean Pierre J Issa

Research output: Contribution to journalArticle

Abstract

Background: Sporadic colorectal cancers often arise from a region of cells characterized by a "field defect" that has not been well defined molecularly. DNA methylation has been proposed as a candidate mediator of this field defect. The DNA repair gene O6 -methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal cancer. We hypothesized that MGMT methylation could be one of the mediators of field cancerization in the colon mucosa. Methods: We studied MGMT promoter methylation by three different bisulfite-based techniques in tumor, adjacent mucosa, and nonadjacent mucosa from 95 colorectal cancer patients and in colon mucosa from 33 subjects with no evidence of cancer. Statistical tests were two-sided. Results: MGMT promoter methylation was present in 46% of the tumors. Patients whose cancer had MGMT promoter methylation also had substantial MGMT promoter methylation in apparently normal adjacent mucosa. This methylation was seen with a quantitative assay in 50% (22/44; 95% confidence interval [CI] = 34% to 65%) of normal samples with MGMT promoter methylation in the adjacent tumors, 6% (3/51; 95% CI = 1% to 16%) of samples without MGMT methylation in adjacent tumors, and 12% (4/33; 95% CI = 3% to 28%) of control samples (P

Original languageEnglish (US)
Pages (from-to)1330-1338
Number of pages9
JournalJournal of the National Cancer Institute
Volume97
Issue number18
DOIs
Publication statusPublished - Sep 2005
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Shen, L., Kondo, Y., Rosner, G., Xiao, L., Hernandez, N. S., Vilaythong, J., ... Issa, J. P. J. (2005). MGMT promoter methylation and field defect in sporadic colorectal cancer. Journal of the National Cancer Institute, 97(18), 1330-1338. https://doi.org/10.1093/jnci/dji275