DNA structure [Illustrative].
A blood test developed at the Hebrew University and Hadassah-University Medical Center using patterns of circulating DNA from dying cells can detect diabetes, multiple sclerosis, pancreatic cancer, pancreatitis and brain damage, opening up vast possibilities for diagnostic medicine.
The advance was published in Proceedings of National Academy of Sciences and performed by an international team led by HU’s Dr. Ruth Shemer and Prof. Yuval Dor from HU and the hospital’s Prof. Benjamin Glaser.
Testing a total of 320 patients and controls, researchers developed a blood test that can detect multiple pathologies, including diabetes, cancer, traumatic injury and neuro degeneration in a highly sensitive and specific manner.
The novel method identified cell death in specific tissue from methylation patterns of circulating DNA that is released by dying cells.
The DNA of each cell type carries a unique chemical modification called methylation, a process in which methyl groups are added to DNA and change its function.
The methylation patterns of DNA account for the identity of cells (the genes that they express) are similar among different cells of the same type and among individuals and are stable in healthy and disease conditions.
For example, the DNA methylation pattern of pancreatic cells differs from the pattern of all other cell types in the body.
The blood test detects cell death in specific tissues by combining two important biological principles. First, dying cells release fragmented DNA to the circulation, where it travels for a short time. This fact has been known for decades, but because the DNA sequence of all cells in the body is identical, it has not been possible to determine the tissue of origin of circulating DNA, and simple measurement of the amount of circulating DNA is of limited use.
The researchers identified multiple DNA sequences that are methylated in a tissue- specific and can serve as biomarkers for the detection of DNA derived from each tissue. They then developed a method to detect these methylated patterns in DNA circulating in blood, and demonstrated its utility for identifying the origins of circulating DNA in different human pathologies, as an indication of cell death in specific tissues. They were able to detect evidence for pancreatic beta-cell death in the blood of patients with new-onset type 1 diabetes, oligodendrocyte death in patients with relapsing-remitting multiple sclerosis, brain-cell death in patients after traumatic or ischemic brain damage, and exocrine pancreas cell death in patients with pancreatic cancer or pancreatitis.
“Our work demonstrates that the tissue origins of circulating DNA can be measured in humans. This represents a new method for sensitive detection of cell death in specific tissues, and an exciting approach for diagnostic medicine,” said Shemer, a DNA methylation expert and one of the lead authors of the new study.
“In the long run, we envision a new type of blood test aimed at the sensitive detection of tissue damage, even without a priori [independent of experience] suspicion of disease in a specific organ. We believe that such a tool will have broad utility in diagnostic medicine and in the study of human biology,” said Benjamin Glaser, head of the hospital’s endocrinology department and another lead author of the study.
HU cancer researcher Prof.
Howard Cedar, a study co-author, commented that the paper “presents a completely new approach to diagnosing diseases with enormous potential. It’s based on an ingenious idea that one can detect tissue-specific DNA in the bloodstream by taking advantage of the fact that each tissue has a unique methylation pattern. The method can be used to detect cell death in the body and therefore reveal many different diseases even before the symptoms appear.”
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