DIA-CHIP

ChIP and MIRA for clinical diagnosis

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 Obiettivo del progetto (Objective)

'DIA-ChIP seeks to develop state-of-the-art molecular techniques for the routine high-throughput analysis of clinical samples for advanced molecular diagnosis and biomedical research. This will be achieved through a collaborative partnership between academic, SME and public health partners interacting through the IAPP, and the secondments and recruitments it supports. New molecular diagnostics in clinical pathology need to be robust, cost effective and offer significant advantages over existing techniques. With the move towards personalised medicine the specificity of diagnosis will need to be enhanced significantly, yet in the short to medium term will need to be compatible with current gold standards of analysis. In this project the focus will be on the most important cancer affecting the female European population – Breast Cancer. The ability to analyse archived clinical material is currently limited to immuno-histochemistry and quantification the native biomolecules (DNA, RNA, protein). The advent of functional characterisation of these molecules i.e. DNA-protein interactions and DNA status will provide information to enhance diagnostic histopathology. Application to archival material will provide access to a hugely valuable resource and will contribute significantly to scientific understanding of disease processes by allowing the examination of large patient cohorts, and by facilitating direct comparison to model systems. Also by examining patient samples in concert with model human cell culture systems, alternatives to animal model systems will be developed. DIA-ChIP features the creation of a strategic partnership between 4 groups that is critical in realising the project. The partners will develop strong long-term collaborative links for future research projects and intellectual exchange that will serve to strengthen each of the partners positions. The ultimate aim is to ensure long-term co-operation between all sectors -Business, Academic, Public Health'

Introduzione (Teaser)

Molecular epigenetics diagnostics are the new frontier in clinical pathology. An EU-funded project developed new epigenetic techniques to diagnose endometrial cancer and better understand the related technology.

Descrizione progetto (Article)

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.