Multidisciplinary approach for groundbreaking study on tumor epigenetics

29 October 2016
A group of researchers lead by Diether Lambrechts (VIB-KU Leuven) explored the mechanisms that cause increased levels of methylation in tumor genes — information that is vital to the adaptation of therapies to fight different types of tumors. Methylation is one of the ways that gene expression is different in tumor cells, which leads to different conditions inside a tumor. One of the changes that occur in solid tumors is a lack of oxygen, or hypoxia, which leads to the spread of the disease to other parts of the body.

Cancers usually start with a single cell that has mutated, and the mechanisms that are behind these mutations are well-known. Tumors are not only different from their tissues of origin genetically, but also epigenetically, which has to do with the way genes are expressed rather than the genes themselves. Bernard Thienpont, a postdoctoral researcher who collaborated on the study, gives us inside info about the boundary-breaking research, which was published in Nature.

Bernard, what are the significant lessons learned?
Bernard: “There are two that really stand out to me. The first is that the environment inside a tumor can have a huge impact on the way genes are expressed, and the second is that epigenetic mutations do exist. The second one is notoriously difficult to demonstrate, and we managed to go a long way towards proving that genetic changes aren’t required to cause epigenetic changes in a tumor. These understandings give us more insight into the tumor development process, potentially leading to new, inexpensive and reliable detection methods and more targeted therapies.”

What did you find was the most important experience in this project?
Bernard: “Our investigations crossed the borders of many disciplines, and I found this especially enriching. The combined proof that was delivered in each of these different biomedical domains really pushed our research forward tremendously, and inspired trust in ourselves and in our reviewers to accept our findings. “Multidisciplinarity” isn’t just a science buzzword – for this project, intersections between domains were crucial to our success.”

What was one of the major challenges?
Bernard: “Understanding a key reaction on a kinetic level was the most challenging, since the enzymes we were studying were not stable, and the reaction conditions had to be very specific. It was tough to fine tune each of the reaction components to develop a reproducible experiment.”

Do you have any good anecdotes about the project?
Bernard: “I was always surprised that nobody else had really explored this idea, since it was such an obvious line of investigation for me. Interestingly, a group from Chicago already studied this mechanism, but in the one cell type that turned out to be the exception to the rule. We were lucky not to be scooped!”

Thienpont, Steinbacher, Zhao, D’Anna et al., Nature 2016

Bernard Thienpont (VIB-KU Leuven)