Analysis of Fecal DNA Methylation to Detect Gastrointestinal Neoplasia

Overview

Journal J Natl Cancer Inst

Publisher Oxford University Press

Specialty Oncology

Date 2009 Aug 25

PMID 19700653

Citations 59

Authors

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

Affiliations

Soon will be listed here.

Abstract

Background: The 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.

Methods: We 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.

Results: Analysis 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).

Conclusions: Methylation 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.

Citing Articles

Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications.

Cao Q, Tian Y, Deng Z, Yang F, Chen E Int J Mol Sci. 2024; 25(6).

PMID: 38542332 PMC: 10969857. DOI: 10.3390/ijms25063358.

Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration.

Oh C, Cho Y Intest Res. 2024; 22(2):131-151.

PMID: 38295766 PMC: 11079515. DOI: 10.5217/ir.2023.00115.

Circulating cell-free DNA methylation patterns as non-invasive biomarkers to monitor colorectal cancer treatment efficacy without referencing primary site mutation profiles.

Yasui K, Toshima T, Inada R, Umeda Y, Yano S, Tanioka H Mol Cancer. 2024; 23(1):1.

PMID: 38172877 PMC: 10762960. DOI: 10.1186/s12943-023-01910-y.

DNA methylation drives a new path in gastric cancer early detection: Current impact and prospects.

Wang X, Dong Y, Zhang H, Zhao Y, Miao T, Mohseni G Genes Dis. 2023; 11(2):847-860.

PMID: 37692483 PMC: 10491876. DOI: 10.1016/j.gendis.2023.02.038.

An overview of DNA methylation markers for early detection of gastric cancer: current status, challenges, and prospects.

Xue Y, Huang C, Pei B, Wang Z, Dai Y Front Genet. 2023; 14:1234645.

PMID: 37560387 PMC: 10407555. DOI: 10.3389/fgene.2023.1234645.

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