Fig. 3

Gene function and a good marker gene. Genes 4 and 5 are tumor-suppressor genes and, when both are methylated, cell transformation takes place. a In a normal tissue, no or little methylation is present. b After exposure to a carcinogenic factor, such as chronic inflammation, specific genes become methylated. Good marker genes (genes 2 and 3) are those readily methylated upon exposure to the carcinogenic factor in association with the methylation of tumor-suppressor genes, which are generally resistant to methylation. Specific methylation of genes 2 and 3, not gene 1, is a candidate marker for exposure to the carcinogenic factor. c After repeated exposure to the carcinogenic factor, the fractions of cells with methylated marker genes increase, and some cells (cell no. 2) can acquire methylation of multiple tumor-suppressor genes and transform