A team of researchers at the IDIBELL (Bellvitge Biomedical Research Institute of Barcelona, Spain), have become the first to describe the DNA methylation of Ewing sarcoma cells. In doing so, this research has identified a protein, known as PTRF, which appears to be a promising treatment option for Ewing sarcoma patients in the future.

What is DNA Methylation?

DNA methylation is a complex process which modifies the DNA in order to control gene expression. The modifications this methylation process create result in certain genes being turned on or turned off. Controlling which genes are turned on or off allows the activation, or perhaps blocking, of certain characteristics and functions a cell may have. Therefore, the DNA methylation process may trigger certain cell processes that lead to the development of diseases, such as cancer, as the characteristics and functioning of the cell becomes abnormal.

How does this relate to Ewing sarcoma?

Identifying DNA methylation is an exciting research area in many diseases, and particularly in cancer. Dr Martinez-Tirado and the sarcoma research group at IDIBELL are the first to successfully investigate this process in Ewing sarcoma cells, and the results have been very beneficial. One gene affected by DNA methylation that caught the attention of the research team was a protein that influences the production of PTRF.

PTRF is a protein linked to the formation of a cell structure known as caveolae - which are very small pouches on the surface of the cells outer layer. Caveolae are involved in controlling cell processes; such as the entry of molecules into the cell and cell signalling pathways. Normal, healthy, cells are seen to present with this caveolae structure. However, this research concluded that Ewing sarcoma cells do not have caveolae, or express PTRF, which affects the cell-signalling processes taking place in these cancerous cells.

What does this research finding mean for patients?

Further analysis of patient samples led the research team to discover an expression of PTRF and caveolae to relate to a better patient survival. This suggests that identifying PTRF may be a predictor of individual patients’ outlook and survival aspects. Furthermore, re-introducing PTRF into Ewing sarcoma cells instigates the formation of the caveolae and allows cell signalling processes to be triggered.

This research found that the introduction of PTRF, and therefore caveolae, activated the signalling pathway of p53 – a well-known tumour suppressor which activates the process of cell death. Therefore, if PTRF can trigger this tumour suppressor in Ewing sarcoma cells, introducing PTRF promises to be a potential therapeutic option in patients due to its ability to destroy these cancerous cells.

This research is in the very early stages and there are many aspects to consider in regard to the gene expression of individual patients for this possible therapeutic measure to be successful. Therefore, this therapy will be investigated as a potential ‘personalised therapy’; a treatment that is used following the examination of the individual patients gene expression and specific information about their tumour before determining if such as treatment would be successful and beneficial to that patient.