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Targeted Microarrays for 5-hydroxymethylcytosine-based Diagnosis of Hematological Malignancies

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.

Coordinator

TEL AVIV UNIVERSITY
Net EU contribution
€ 150 000,00
Address
Ramat Aviv
69978 Tel Aviv
Israel

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Activity type
Higher or Secondary Education Establishments
Other funding
No data