Epigenetics of cancer

Cancer signatures extend to epigenetic marks. Credits: Ana Costa

Cancer's new signatures:

Epigenetic modifications are conserved among various metastases in the same person.

Today’s EpiPost focuses on a new discovery concerning prostate cancer and its metastases. The report published in Science Translational Medicine (23rd January 2013 ) highlights the need for personalized medicine by showing that the patterns of epigenetic modifications vary considerably between lethal prostatic tumours from different men but are maintained within the tumour and metastases in the same person.

Epigenetics is the layer of genomic regulation that is not due to the sequence of As, Ts, Cs and Gs in the DNA molecule, but instead relies on chemical marks found in nuclear DNA and its associated proteins. These epigenetic marks that sit on DNA, namely the methylation mark, are very relevant from the point of view of physiology, as they may shape to the way cells responds to stimulus, both from outside, and from inside the cell itself. In recent years, scientists have observed that tumours display their own patterns of DNA methylation and those differ from the ones found in the “normal” cells of the same person. This observation led to the question: can DNA methylation be used as a diagnostic biomarker for cancer?

So far, the general belief that DNA methylation patterns varied too much in each patient's widespread cancers procrastinated the development of diagnostic strategies or even therapies. Now, with the help of new biochemical and computational technologies, scientists from the Johns Hopkins University, in Baltimore, USA, made two seminal observations that may change this view: first, that the DNA methylation patterns were considerably altered between tumours from different individuals; and second, that tumours and metastases from the same individual had identical DNA methylation patterns. For this analysis, the samples were obtained from autopsies of men who had died of metastatic prostate cancer. Both samples from the various metastases, as well as samples from normal tissues were collected for genomic comparisons.

The results led the scientists to conclude that each cancer evolves to acquire its own characteristic signature of DNA modifications, and that this epigenetic signature is maintained at sites of metastases. This observation has a close parallel to what is known about genetic alterations of tumours, which are also stable within each individual. As with genetic alterations that contribute to the onset and dissemination of cancer, epigenetic changes are also to be taken into account when investigating the events leading to cancer progression.

The new data revealed that new biomarkers of aggressive cancers lie in the epigenetic landscapes of each patient’s cancer cells. Scientists believe that this knowledge will help in the early identification of these forms of cancer and may possibly contribute to the development of therapeutic strategies directed at each person’s specific cancer epigenetic signatures.