Silencing of genes by hypermethylation contributes to cancer progression and has 
been shown to occur with increased frequency at specific genomic loci. However, 
the precise mechanisms underlying the establishment and maintenance of aberrant 
methylation marks are still elusive. The de novo DNA methyltransferase 3B 
(DNMT3B) has been suggested to play an important role in the generation of 
cancer-specific methylation patterns. Previous studies have shown that a 
reduction of DNMT3B protein levels induces antiproliferative effects in cancer 
cells that were attributed to the demethylation and reactivation of tumor 
suppressor genes. However, methylation changes have not been analyzed in detail 
yet. Using RNA interference we reduced DNMT3B protein levels in colon cancer 
cell lines. Our results confirm that depletion of DNMT3B specifically reduced 
the proliferation rate of DNMT3B-overexpressing colon cancer cell lines. 
However, genome-scale DNA methylation profiling failed to reveal methylation 
changes at putative DNMT3B target genes, even in the complete absence of DNMT3B. 
These results show that DNMT3B is dispensable for the maintenance of aberrant 
DNA methylation patterns in human colon cancer cells and they have important 
implications for the development of targeted DNA methyltransferase inhibitors as 
epigenetic cancer drugs.