Cancer is an epigenetic disease
It is now clear that cancer is an epigenetic disease. In most
tumors the DNA methylation pattern is defective. Vast regions of the genome
lose their methylation while specific regions are heavily methylated.
Understanding the mechanisms that link chromatin structure and DNA methylation
are extremely important for unraveling the possible mechanisms responsible
for the DNA methylation pattern in normal tissues, possible physiological
alterations of DNA methylation patterns throughout life and during the aging
process, and its aberration in cancer. Before we are able to properly target
DNA methylation in cancer therapy we ought to understand which of the changes
in the DNA methylation machinery and DNA methylation pattern are causal for
cancer and which are a consequence of the transformation process.
My laboratory is interested in understanding the links between
chromatin, DNA methylation and cancer therapy. We want to understand what
mechanisms define the DNA methylation pattern and why is the DNA methylation
pattern tightly correlated with chromatin structure. Our working hypothesis
is that both the DNA methylation and demethylation machineries are directed
by chromatin structure and that both are defective in cancer. We want to understand
how chromatin directs DNA methyltransferase and demethylase and how why they
are involved in cancer and metastasis.