[Developing technologies for epigenomic analysis and clinical application of molecular diagnosis]

Epigenetic alterations such as DNA methylation play a key role in silencing genes in carcinogenesis. DNA methylation leads to the silencing of a variety of genes involved in cell-cycle control, apoptosis, cell signaling and DNA repair in gastrointestinal cancer. The recent development of methylation analysis offers a quantitative, high sensitivity, high throughput and reliable method. This approach enabled us to apply methylation analysis in a clinical setting. The miR-34b/c gene is a tumor suppressor that is frequently silenced by DNA methylation in colorectal and gastric cancer (GC). Accurate preoperative diagnosis of invasiveness is essential for selecting appropriate therapeutic options for colorectal cancer, but the distinction between invasive and non-invasive colorectal tumor is often difficult. Methylation levels of miR-34b/c in colorectal washing fluid were highly discriminative between invasive and non-invasive tumors. Previous reports show that H. pylori infection, which plays an important role in gastric carcinogenesis, induces the methylation of various genes in the noncancerous gastric mucosae. These finding suggest that the accumulation of aberrant DNA methylation in noncancerous gastric mucosa is involved in the epigenetic field defect. Methylation of miR-34b/c was significantly elevated in noncancerous gastric mucosae of multiple GC patients compared with those of single GC patients and H. pylori-positive healthy individuals. These results suggest that methylation might be a useful marker for the diagnosis and risk assessment of cancer.