Genomic hypomethylation is one of the most common molecular events in the multistep carcinogenesis (1-5). This epigenetic process results in chromosomal instability (6-9), increased mutation events (10), and altered gene expression (11). Recently, we explored general characteristics and consequences of the global hypomethylation by evaluating methylation statuses of long interspersed element-1 (L1) repetitive sequences (3, 12, 13). Our recent publication in Nucleic Acids Research (13) also the first who described methylation statuses of endogenous DNA double strand breaks (EDSBs) and proposed EDSBs as a possible linkage between global hypomethylation and genomic instability (13). Our ongoing researches are the roles of L1 methylation in cancer. We are exploring the mechanisms if and how L1 methylation controls gene expression and chromosomal instability.