Abstract:
Genome-wide losses of DNA methylation, global genomic hypomethlation, is a common epigenetic change in malignancies. In mammalian genome, the bulk of cytosine methylation occurs on repetitive element. Long Interspersed Nuclear Elements-1 (LINE-1), a highly repeated, interspersed human retrotransposon, constitutes about 17% of the human genome. This study evaluates the methylation status of LINE-1 by newly established methylation specific PCR method, combined bisulfite restriction analysis (COBRA), in the microdissected paraffin materials from various normal and neoplastic human tissues. Results hypomethylation of LINE-1 consisten in leukocytes from different age and gender. However, in normal tissues from different organs showed tissue specific levels of methylated LINE-1 sequences. A significantly increased percentage of hypomethylation has been observed in several carcinomas including breast, colon, lung, head and neck, bladder, esophagus, liver, prostate, and stomach. Similarly, DNA derived from sera of gastric cancer patients displayed more hypomethylated LINE-1 than those of control sera. In a colorectal carcinogenesis model of multistep process detected significantly greater hypomethylation in carcinoma than those of dysplastic polyp and histological normal colonic epithelium. In conclusion these results suggested that normal tissue-specific difference in DNA methylation pattern and cancer associated global hypomethylation of LINE-1 may progressively evolve during multistage carcinogenesis.
