Methylation status of normal background mucosa is correlated with occurrence and development of neoplasia in the distal colon.
The aim of this study is to evaluate the methylation status of normal colonic mucosa in relation to the stage of neoplasia arising from the mucosa. The methylation status of 2 age-related loci (ESR1 and MYOD1) and global methylation (the mean of Alu and Sat2) in the normal colonic mucosa of 156 patients with and without colorectal neoplasia were examined. The distal colon and proximal colon were analyzed separately because neoplasia is biologically and clinically different between these sites. The methylation status was determined by MethyLight using percentage of methylated reference (PMR). In the distal colon, methylation of the age-related loci decreased as the stage of neoplasia increased (patients with no neoplasia or with adenoma < or =9 mm versus patients with advanced adenoma or with invasive cancer: ESR1-PMR median, 21.0 versus 15.7; P = .015; MYOD1-PMR median, 5.35 versus 3.80; P = .0037, respectively). Interestingly, global methylation was inversely correlated with the stage of neoplasia (59.7 versus 61.5; P = .054). In contrast, the proximal colon showed no significant correlations. The methylation of MYOD1 in the normal mucosa was significantly correlated with K-ras mutation in neoplastic tissue arising from the mucosa. Specific epigenetic changes in normal colonic mucosa may be correlated with the occurrence and development of neoplasia in the distal colon.
Hiraoka
Sakiko
S
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Kato
Jun
J
Horii
Joichiro
J
Saito
Shunsuke
S
Harada
Keita
K
Fujita
Hideyuki
H
Kuriyama
Motoaki
M
Takemoto
Koji
K
Uraoka
Toshio
T
Yamamoto
Kazuhide
K
D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein