Aberrant DNA methylation in intestinal metaplasia

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DNA methylation plays an essential role in embryonic development, and, in this process, a tissue-specific DNA methylation pattern is formed under precise regulation. Therefore, aberrant DNA methylation might also be involved in a polyclonal disorder in which abnormal differentiation is involved. As a typical disorder of differentiation, we focused on intestinal metaplasia (IM) of the stomach, in which multiple gastric glands aberrantly differentiate into those with intestinal characteristics. By MS-RDA, we identified four genes silenced in gastric glands that have undergone IM (Mihara et al., 2006). Among the four genes, aberrant methylation of ZIK1 was consistently present in glands with IM, even if the glands were isolated from physically distant positions within the stomach (Fig. ). This was one of the earliest studies that showed involvement of epigenetic abnormality in disorders with polyclonal origins.


Fig. Gastric glands with intestinal metaplasia have aberrant DNA methylation of ZIK1