Aberrant DNA methylation causes cancer. Wait, didn’t we know this already? Well, not exactly. Association and causation are two very different things. For instance, being smart may be associated with wearing glasses, but the actual cause is a desire to not bump into everything.
In order to determine whether aberrant DNA methylation at particular loci can play a causal role in tumorigenesis, a team of researchers from Taiwan and Ohio developed a novel method. Here is how they did it and what they found:
- Using Targeted DNA Methylation (TDM), they recruited DNA methyltransferases (DNMTs) to specific loci by introducing methylated DNA complementary to the target.
- Concurrent DNA methylation at tumor suppressor genes RASSF1A and HIC1 in human mesenchymal stem cells (MSCs) resulted in the acquisition of cancer initiating/cancer stem cell features both in vitro and in a xenograft model.
- The transformed cells had genome-wide changes in DNA methylation and altered p53 function.
- The tumorigenic phenotype was reversed by treatment with a DNMT inhibitor.
This is the first demonstration that silencing of particular tumor suppressor genes (TSGs) by aberrant DNA methylation can directly cause somatic stem cells to transform into cancer stem cell (CSC)-like cells. Hopefully their findings will finally and heritably silence the critics.
Determine whether there is a causal link for yourself at Cancer Research, April 2011.