Analysis of fecal DNA methylation to detect gastrointestinal neoplasia

Takeshi Nagasaka, Noriaki Tanaka, Harry M. Cullings, Dong Sheng Sun, Hiromi Sasamoto, Takuyuki Uchida, Minoru Koi, Naoshi Nishida, Yoshio Naomoto, C. Richard Boland, Nagahide Matsubara, Ajay Goel

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

BackgroundThe development of noninvasive screening tests is important to reduce mortality from gastrointestinal neoplasia. We sought to develop such a test by analysis of DNA methylation from exfoliated cancer cells in feces.MethodsWe first analyzed methylation of the RASSF2 and SFRP2 gene promoters from 788 primary gastric and colorectal tissue specimens to determine whether methylation patterns could act as stage-dependent biomarkers of gastrointestinal tumorigenesis. Next, we developed a novel strategy that uses single-step modification of DNA with sodium bisulfite and fluorescence polymerase chain reaction methodology to measure aberrant methylation in fecal DNA. Methylation of the RASSF2 and SFRP2 promoters was analyzed in 296 fecal samples obtained from a variety of patients, including 21 with gastric tumors, 152 with colorectal tumors, and 10 with non-neoplastic or inflammatory lesions in the gastrointestinal lumen.ResultsAnalysis of DNA from tissues showed presence of extensive methylation in both gene promoters exclusively in advanced gastric and colorectal tumors. The assay successfully identified one or more methylated markers in fecal DNA from 57.1% of patients with gastric cancer, 75.0% of patients with colorectal cancer, and 44.4% of patients with advanced colorectal adenomas, but only 10.6% of subjects without neoplastic or active diseases (difference, gastric cancer vs undiseased = 46.5%, 95% confidence interval (CI) = 24.6% to 68.4%, P <. 001; difference, colorectal cancer vs undiseased = 64.4%, 95% CI = 53.5% to 75.2%, P <. 001; difference, colorectal adenoma vs undiseased = 33.8%, 95% CI = 14.2% to 53.4%, P <. 001).ConclusionsMethylation of the RASSF2 and SFRP2 promoters in fecal DNA is associated with the presence of gastrointestinal tumors relative to non-neoplastic conditions. Our novel fecal DNA methylation assay provides a possible means to noninvasively screen not only for colorectal tumors but also for gastric tumors.

Original languageEnglish
Pages (from-to)1244-1258
Number of pages15
JournalJournal of the National Cancer Institute
Volume101
Issue number18
DOIs
Publication statusPublished - Sep 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Nagasaka, T., Tanaka, N., Cullings, H. M., Sun, D. S., Sasamoto, H., Uchida, T., Koi, M., Nishida, N., Naomoto, Y., Boland, C. R., Matsubara, N., & Goel, A. (2009). Analysis of fecal DNA methylation to detect gastrointestinal neoplasia. Journal of the National Cancer Institute, 101(18), 1244-1258. https://doi.org/10.1093/jnci/djp265