DNA methylation is the epigenetic modification, which introduces 5mC as fifth 
base onto DNA. As for the distribution of 5mCs, it is well known that they 
distribute themselves in a non-random fashion in genomic DNA so that methylation 
pattern is characterized by the presence of methylated cytosines on the bulk of 
DNA while the unmethylated ones are mainly located within particular regions 
termed CpG islands. These regions represent about 1% of genomic DNA and are 
generally found in the promoter region of housekeeping genes. Their unmethylated 
state, which is an essential condition for the correct expression of correlated 
genes, is paradoxical if one considers that these regions are termed CpG islands 
because they are particularly rich in this dinucleotide, which is the best 
substrate for enzymes involved in DNA methylation. Anomalous insertion of methyl 
groups in these regions generally leads to the lack of transcription of 
correlated genes. An interesting scientific problem is to clarify the 
mechanism(s) whereby CpG islands, which remain protected from methylation in 
normal cells, are susceptible to methylation in tumor cells. How the CpG 
moieties in CpG islands become vulnerable or resistant to the action of DNA 
methyltransferases and can thus lose or maintain their characteristic pattern of 
methylation is still an open question. Our aim is to gather some mechanisms 
regarding this intriguing enigma, which, despite all energy spent, still remains 
an unresolved puzzle.