Reduced mRNA expression of the DNA demethylase, MBD2, in human colorectal and stomach cancers

A study was performed to evaluate the significance of aberrations of the newly identified DNA demethylase, MBD2, in human carcinogenesis. Levels of expression of DNA demethylase mRNA were examined by reverse transcription followed by real-time quantitative detection of the PCR products in 32 samples of colorectal cancer tissue, 24 stomach cancers, and the corresponding noncancerous mucosae. DNA demethylase mRNA levels normalized with glyceraldehyde-phosphate dehydrogenase (GAPDH) mRNA were reduced in 31 (97%) of the 32 colorectal cancers and in 22 (92%) of the 24 stomach cancers when compared with the levels in the corresponding noncancerous mucosae. The average levels of DNA demethylase mRNA expression normalized with GAPDH mRNA in each of the colorectal (0.81 +/- 0.55) and stomach (2.88 +/- 0.23) cancers were significantly lower than in the noncancerous mucosae (1.90 +/- 0.16 and 5.11 +/- 0.34, respectively, p < 0.0001). There was no significant association between the DNA demethylase mRNA level and malignant potential in both colorectal and stomach cancers. These data suggest that reduced expression of DNA demethylase may play a role at a certain step of multistage carcinogenesis. Reduction of DNA demethylase mRNA expression may be, if anything, one of the early events of carcinogenesis, but may not participate in the malignant progression of tumors. (C) 1999 Academic Press.