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

104 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

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

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DNA Methylation
Methylation
Colorectal Neoplasms
Stomach
DNA
Neoplasms
Stomach Neoplasms
Feces
Adenoma
Genes
Carcinogenesis
Biomarkers
Fluorescence
Confidence Intervals
Polymerase Chain Reaction
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nagasaka, T., Tanaka, N., Cullings, H. M., Sun, D. S., Sasamoto, H., Uchida, T., ... 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

Analysis of fecal DNA methylation to detect gastrointestinal neoplasia. / Nagasaka, Takeshi; Tanaka, Noriaki; Cullings, Harry M.; Sun, Dong Sheng; Sasamoto, Hiromi; Uchida, Takuyuki; Koi, Minoru; Nishida, Naoshi; Naomoto, Yoshio; Boland, C. Richard; Matsubara, Nagahide; Goel, Ajay.

In: Journal of the National Cancer Institute, Vol. 101, No. 18, 09.2009, p. 1244-1258.

Research output: Contribution to journalArticle

Nagasaka, T, Tanaka, N, Cullings, HM, Sun, DS, Sasamoto, H, Uchida, T, Koi, M, Nishida, N, Naomoto, Y, Boland, CR, Matsubara, N & Goel, A 2009, 'Analysis of fecal DNA methylation to detect gastrointestinal neoplasia', Journal of the National Cancer Institute, vol. 101, no. 18, pp. 1244-1258. https://doi.org/10.1093/jnci/djp265
Nagasaka T, Tanaka N, Cullings HM, Sun DS, Sasamoto H, Uchida T et al. Analysis of fecal DNA methylation to detect gastrointestinal neoplasia. Journal of the National Cancer Institute. 2009 Sep;101(18):1244-1258. https://doi.org/10.1093/jnci/djp265
Nagasaka, Takeshi ; Tanaka, Noriaki ; Cullings, Harry M. ; Sun, Dong Sheng ; Sasamoto, Hiromi ; Uchida, Takuyuki ; Koi, Minoru ; Nishida, Naoshi ; Naomoto, Yoshio ; Boland, C. Richard ; Matsubara, Nagahide ; Goel, Ajay. / Analysis of fecal DNA methylation to detect gastrointestinal neoplasia. In: Journal of the National Cancer Institute. 2009 ; Vol. 101, No. 18. pp. 1244-1258.
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