The promoter methylation status of the DNA repair gene O6-methylguanine-DNA methyltransferase in ulcerative colitis.
Patients with long-standing and extensive ulcerative colitis (UC) have an increased incidence of colorectal cancer (CRC). It has been reported that a DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT) is inactivated by promoter hypermethylation in sporadic CRCs. Hence, we investigated the promoter methylation status of MGMT by methylation specific polymerase chain reaction (PCR) in a total of 67 tissue samples (61 non-cancerous tissues and 6 cancer tissues) from 24 patients with UC. Promoter hypermethylation of MGMT was detected in one well-differentiated adenocarcinoma (16.7%) of 6 cancer samples and not detected in any of adenomas and dysplasias. In non-dysplastic tissues, promoter hypermethylation of MGMT was detected in 2 (3.7%, mucosa with mild inflammation) of 54 samples. The frequency of MGMT promoter hypermethylation in UC-associated CRCs found in this study (16.7%) is obviously lower than previously reported in sporadic CRCs (39.0-42.0%). We also confirmed that 42.9% (6/14) of sporadic CRCs showed the promoter methylation. These findings indicated that promoter hypermethylation of the MGMT gene is infrequent in patients with UC, and may not closely contribute to UC-associated colorectal tumorigenesis. A different genetic pathway for tumor progression may exist between sporadic CRC and UC-associated CRC.
Matsumura
Shunji
S
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551 Hiroshima, Japan.
Oue
Naohide
N
Ito
Reiko
R
Nakayama
Hirofumi
H
Kitadai
Yasuhiko
Y
Yokozaki
Hiroshi
H
Chayama
Kazuaki
K
Yasui
Wataru
W
D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics*; D019175:DNA Methylation; D004260:DNA Repair; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011401:Promoter Regions, Genetic
D019853:O(6)-Methylguanine-DNA Methyltransferase