Epigenetics and Sarcoma

Sometime last year, I had the opportunity to see the excellent 2005 BBC video production, "The Ghost in Your Genes" and the equally wonderful 2007 updated version that aired on the US Public Broadcasting Show, NOVA. Both productions presented excellent and complementary introductions for the layperson to clues that have led scientists to formulate an understanding of epigenetics – a form of genetic control and expression. The BBC and NOVA productions gave examples of how stress and other environmental factors in your ancestors ("genetic imprinting") can affect how genes are switched on or off in your body and examples of how epigenetics may be involved in the development of diseases such as cancer.

After watching these shows, I spent several months looking for articles describing investigations related to epigenetics and cancer or, more specifically, epigenetics and sarcoma. I found, as you might suspect, that almost all such material is located in the scientific literature and therefore is difficult for the average person (with at most an introductory course in biology) to understand without spending a considerable amount of time to gain the background necessary to make sense of the articles. Even with this background, the increasing importance of epigenetics in understanding cancer emerged during my exploration, exemplified by the following three quotations:

1. "Epigenetics, the study of non-DNA sequence-related heredity, is at the epicenter of modern medicine because it can help to explain the relationship between an individual’s genetic background, the environment, aging, and disease. It can do so because the epigenetic state varies among tissues and during a lifetime, whereas the DNA sequence remains essentially the same. As cells adapt to a changing internal and external environment, epigenetic mechanisms can remember these changes in the normal programming and reprogramming of gene activity.¹"

2. "Epigenetic gene silencing is an important mechanism for the loss of gene function and collaborates with genetic mutation in the initiation and progression of human cancer.²"

3. "Finally, we need a better molecular understanding of epigenetic phenomena in human development and disease. ... Moreover, DNA methylation systems and the chromatin machinery that writes and interprets histone modifications are clearly involved in disease states, particularly cancer. ... Despite these uncertainties, therapeutic inhibition of histone deacetylation and DNA methylation is already proving useful in clinical trials of cancer therapies.³"

I propose that researchers in the epigenetics and sarcoma communities meet in the near term in order to define a strategic path for sarcoma-related epigenetics research. Identifying key areas of research and the relationships between them is a critical step toward exploiting epigenetics in the diagnosis, treatment and cure of sarcomas. I recommend that the group also propose a framework (laboratory standards, protocols, infrastructure, data and reporting structures, annual workshops, funding requirements, etc.) for supporting the research and the dissemination of the results.

This framework should encourage collaborative, multi-institutional, focused research projects that draw on the strengths of each institution, as well as research done in small labs focused on specific aspects of investigations. The framework should encourage an open access environment for the sharing and dissemination of results. Government agencies, sarcoma advocacy groups, private foundations, and philanthropic individuals would be approached to collaborate on the funding of the research that is identified as the output of such a research consensus and strategic path identification meeting.