Advancing molecular epigenetics diagnostics
The project 'ChIP and MIRA for clinical diagnosis' (DIA-CHIP) worked to develop state-of-the-art molecular techniques for routine, high-throughput analysis of the epigenetic status of clinical samples, particularly those fixed in formaldehyde/paraffin (FFPE), allowing for advanced molecular diagnosis and biomedical research unlocking the potential for screening large retrospective patient cohorts from clinical archives. The project realised its goals through collaborative partnership among three key sectors: business, academia and public health. New molecular diagnostics need to be robust and cost effective, as well as offer significant advantages over existing techniques. Furthermore, with the move towards personalised medicine, diagnoses need to be far more specific. At this point in time, however, techniques also need to be compatible with current gold standards of analysis. Working within this framework, researchers analysed endometrial cancer samples using DNA methylation detection technology. The researchers' focus was on specific targets, including the oestrogen receptor (ER) and downstream target genes of this important nuclear hormone receptor transcription factor. For the first time, researchers were able to characterise regulation of molecular variants of the ER. The analysis was conducted using a range of techniques, from bisulphite sequencing for high-resolution analysis to MeDIP for low-resolution work. In fact, during the project's duration, MeDIP replaced MIRA as the technique of choice for low-resolution analysis. Other changes in technology occurred during this project. Shortly after it was funded, there was a global explosion in the area of epigenomics. At the same time, rapid development of ChIP-seq technology and DNA sequencing technologies occurred. As a result, microarray screening was replaced by a ChiP-seq approach. Work on refining this technology is ongoing. The project was successful on many fronts. It advanced technologies for utilisation in epigenomics research, an area that grew significantly throughout the project's lifetime. The research resulted in several manuscripts for submission to scientific journals. It resulted in several new products being launched commercially. Finally, the project brought together partners who shared valuable insights and established lasting relationships.
Keywords
Molecular diagnostics, endometrial cancer, clinical diagnosis, oestrogen receptor, epigenomics
