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.

Cancer signatures extend to epigenetic marks. Credits: Ana Costa
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.

From the brains of honeybees, we learned that epigenetics can control social behaviour and career changes.

Honeybee societies have intrigued us for a long time for their intricate organization. Many CEOs would like to know the secrets behind beehives’ structured hierarchy to replicate it in their own companies. More than management theories, neuroscience may be the answer: By studying the epigenetics of bees’ brains, scientists have found not only how the distinct behaviours are controlled, but also that they can be reversed!

While developing, one sister bee can become a queen, while the other sister will be a worker for her entire, considerably shorter, life. How is this achieved if these sisters share the same genetic code? At birth, all honeybees look identical and it is not clear which one will become a queen. In contrast with human royalty, bees do not inherit royal “blood”, meaning that the genes they carry will not dictate their social fate. A paper published back in October of 2012 has revealed that the secret is epigenetics, the alterations in DNA and its associated factors that are independent of the sequence of DNA itself. We all know that DNA is made of As and Ts, Cs and Gs, and even if we do not know what they mean, we understand that these letters form codes and those codes control the way organisms function. While studying the brains of honeybees, scientists have discovered that the DNA letters may be shared by a queen and a worker in the same hive; however, there are particular changes found in those letters that make all the difference*. Those are the epigenetic changes, in particular the epigenetic mark called DNA methylation.

Whereas the difference between queens and workers could not be explained in the referred paper, differences between workers with different roles in society became more obvious. For that, scientists compared the brains of nurses with the brains of foragers to conclude that DNA methylation was different between these two subcastes. More importantly, when foragers were compelled to switch to nurses, DNA methylation switched as well. The authors concluded that there are epigenetic patterns associated with the different subcastes and that those are reversible.

There are at least two reasons for this to be one of the most important pieces of work published recently, and you may be guessing why… One, these observations are fundamental in that they explain the principles through which different characteristics – behavioural, morphological, of lifespan – can arise from the same sequence of DNA. Two, they are seminal because they showed for the first time that well-defined, securely-established patterns of behaviour are not free from change: epigenetics carries the key to life’s turning points, which may include your long-awaited career change.

*The conventional definition of Epigenetics implies heritability through generations; here, the concept is used in a more “relaxed” way, meaning that the need for inheritance is not stressed.

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