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.

O 6 -methylguanine-DNA methyltransferase (MGMT) is a DNA repair gene which is frequently methylated in colorectal cancer (CRC). However, it remains controversial whether methylation of specific CpG sequences within MGMT promoter leads to loss of its protein expression, and if MGMT methylation correlates with G to A transition mutations in KRAS. Two methylation sensitive regions (Mp and Eh region) of MGMT promoter were investigated in 593 specimens of colorectal tissue: 233 CRCs, 104 adenomatous polyps (AP), 220 normal colonic mucosa from CRC patients (N-C) and 36 normal colonic mucosa specimens obtained from subjects without colorectal neoplasia (N-N) by combined bisulfite restriction analysis (COBRA). The region-specific methylation data were compared to the MGMT protein expression, spectrum of KRAS mutations and other clinical features. Extensive (including both Mp and Eh) and partial (either Mp or Eh) MGMT methylation were found in 24.5% and 11.6% of CRCs, 3.8% and 27.9% of APs, 0.5% and 7.7% of C-Ns and 2.8% and 2.8% of N-Ns, respectively. Extensive methylation of MGMT promoter was primarily present in CRCs while partial methylation was common in APs. Extensive methylation of MGMT promoter was associated with loss/reduced protein expression (p < 0.0001), as well as with G to A mutations in KRAS (p 5 0.0017). We herein provide first evidence that extensive methylation of MGMT promoter region is essential for methylation-induced silencing of this gene. Our data suggest that MGMT methylation may evolve and spread throughout the promoter in a stepwise manner as the colonic epithelial cells progress through the classical-adenoma-cancer multistep cascade. ' 2008 Wiley-Liss, Inc.Key words: O 6 -methylguanine-DNA methyltransferase; KRAS mutations; promoter methylation; colorectal cancer; adenomatous polyps O 6 -methylguanine-DNA methyltransferase (MGMT) is a DNA repair gene which removes promutagenic O 6 -methylguanine (O 6 -MeG) residues from DNA and is considered an important predictive factors for chemoresistance in human cancers. [1][2][3][4][5] Loss of MGMT function permits the increased accumulation of O 6 -MeG in DNA, which promotes tumorigenesis through G:C to A:T transition mutations in growth regulating genes such as KRAS and p53. 6-9 Mutations in MGMT have rarely been found, and it has been suggested that MGMT inactivation is primarily manifested through hypermethylation-induced silencing of its promoter in human cancers, including those of the colon and rectum. 5,[9][10][11][12][13][14] However, the associations between MGMT methylation and G to A transition mutations has not been consistently reproduced in different studies. 15,16 Central to this controversy is the fact that there is a lack of clear understanding for precise relationships between methylation of specific MGMT promoter regions and its relationship with the loss of protein expression.It is becoming increasingly clear that the distribution of methylated cytosines in the CpG islands of promoters is not uniform, and the regions most importan...

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A 37-year-old woman suffering from left upper abdominal pain after dinner on April 17, 1999 was admitted to another hospital on April 18 because the pain intensified. A fist-sized lump with tenderness was palpated in the left lower abdomen on admission. But the lump disappeared after the patient vomited during the night and the pain was relieved. On April 19, ileus due to paraduodenal hernia was suspected from abdominal X-rays and CT scan, and the patient was referred to our hospital for elective surgery. At surgery performed on April 20, a hernia opening 2cm in diameter was present in the right side of the Treitz's ligament, through which about a 90cm leugth of the jejunum had invaginated into the mesenter ium of transverse colon. The jejunum entered into the hernia cavity was returned to the normal position, and the opening was closed. She developed adhesive ileus after the operation but it improved without further operation. She was discharged from the hospital on May 16.A case of paraduodenal hernia, that is a rare inner hernia, is here reported, together with a study of similar cases in Japan.

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