TY - JOUR
T1 - Analysis of fecal DNA methylation to detect gastrointestinal neoplasia
AU - Nagasaka, Takeshi
AU - Tanaka, Noriaki
AU - Cullings, Harry M.
AU - Sun, Dong Sheng
AU - Sasamoto, Hiromi
AU - Uchida, Takuyuki
AU - Koi, Minoru
AU - Nishida, Naoshi
AU - Naomoto, Yoshio
AU - Boland, C. Richard
AU - Matsubara, Nagahide
AU - Goel, Ajay
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70349251628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349251628&partnerID=8YFLogxK
U2 - 10.1093/jnci/djp265
DO - 10.1093/jnci/djp265
M3 - Article
C2 - 19700653
AN - SCOPUS:70349251628
SN - 0027-8874
VL - 101
SP - 1244
EP - 1258
JO - Cancer chemotherapy reports. Part 1
JF - Cancer chemotherapy reports. Part 1
IS - 18
ER -
