Epigenomic signatures in the brain
Research type
Research Study
Full title
Identifying circulating epigenomic biomarkers that inform upon the cell of origin in central nervous system pathology
IRAS ID
224312
Contact name
Adel Helmy
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Duration of Study in the UK
3 years, 11 months, 29 days
Research summary
Damaged and dying cells release DNA into the circulation. This circulating, cell-free DNA (cfDNA) can be easily detected in blood and other bodily fluids such as urine and in some conditions in the cerebrospinal (brain) fluid. The amount of DNA present in the blood increases in conditions such as cancer, tissues trauma, stroke, myocardial infarction, inflammatory conditions.
Epigenomics is a term used to describe a number of modification to the DNA and to the proteins that scaffold the DNA (histones). These modifications (methylation and hydroxymethylation) change gene expression without changing the DNA sequence. Each cell type carries specific DNA modifications i.e. epigenomic marks which correlate with its gene-expression profile and are fundamental in the determination of tissue identity. Epigenomic patterns are unique to each cell type, are conserved among cells of the same type in the same individual and among individuals, and are highly stable under physiologic or pathologic conditions. When DNA is released into the circulation, it carries these epigenomic marks. Testing the cfDNA in a blood, urine or brain fluid sample allows us to identify these marks which then inform us of the tissue of origin.
The development of minimally invasive methods to detect and monitor tumours, neuroinflammatory and neurodegenerative conditions continues to be a challenge. cfDNA is emerging as a biomarker that has diagnostic, prognostic and predictive potential in these instances.
Using epigenomic signatures of DNA provides more precise information about the cell type of origin. Further research is needed to accurately define the epigenomic profile of the main cell lineages in the central nervous system. This would maximize the sensitivity and specificity of circulating epigenomes for diagnostic, prognostic and predictive purposes.
We will explore if we can differentiate between the different cell lineages in the human brain based on their epigenomic profile. We shall subsequently use our experience in obtaining cfDNA to identify epigenomic signatures within the plasma, urine of cerebrospinal fluid of individuals with multiple central nervous system related diseases (brain tumours, stroke, trauma)REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
17/EE/0485
Date of REC Opinion
26 Feb 2018
REC opinion
Further Information Favourable Opinion