Project description
Biomarkers for hematological malignancies
Epigenetic modification of cytosine residues on DNA are indicative of gene transcription modulation. 5-hydroxymethylcytosine (5hmC) is the first step of lifting the gene repressive 5-methylcytosine (5mC) mark and may serve as a biomarker for disease. Funded by the European Research Council, the BASE6 project is interested in developing a DNA chip for the analysis of 5hmC distribution in health and disease. The generated platform will be provided at a reduced cost and is expected to fuel research into the discovery of cancer and other disease biomarkers. Long-term, the BASE6 solution will be applied in diagnostics as well as for monitoring disease therapy.
Objective
5-hydroxymethylcytosine (5hmC) is an oxidized form of 5-methylcytosine (5mC). It is the first step of reversing DNA methylation and an important indicator of dynamic epigenetic changes in genomic DNA. One characteristic of cancerous transformations is dramatic modulation of the epigenomic landscape. Consequently, changes in the distribution of 5hmC have been shown to correlate with a broad range of cancers and is potentially a powerful disease biomarker. Nevertheless, existing methods for mapping 5hmC are complex and expensive thus hindering the translation of 5hmC research into clinical use. This project aims at developing a custom DNA chip for 5hmC that will allow cost-effective and targeted analysis of disease biomarkers. We will use our patented procedure for direct fluorescent labeling of 5hmC in combination with commercially available genome-wide microarrays to create maps of 5hmC distribution in health and disease. These large-scale arrays will be used in the discovery phase to identify cancer biomarkers. In the second phase, only the subset of genomic loci that contain medically significant modulation in 5hmC will be used to design and print a custom microarray containing only the relevant probes. This concept predicts a cost reduction of 10-100 fold which will remove the barriers for large scale research and high volume testing. Disease specific diagnostic chips are attractive products with direct impact on society and economy via promoting more accessible testing and patient management. Our preliminary results indicate that we will be able to offer a universal platform for even the most challenging samples including cell-free DNA analysis from liquid biopsies. We envision it as an enabling technology for 5hmC research, biomarker discovery and companion diagnostics for guiding and monitoring therapy.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
69978 Tel Aviv
Israel