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Multiple Diseases Detected via DNA Released from Dying Cells

By LabMedica International staff writers
Posted on 30 Mar 2016
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Image: Schematic diagram of circulating methylated cell free DNA (Photo courtesy of Huntsman Cancer Institute).
Image: Schematic diagram of circulating methylated cell free DNA (Photo courtesy of Huntsman Cancer Institute).
A blood test has been developed that can detect multiple pathologies, including diabetes, cancer, traumatic injury and neurodegeneration, in a highly sensitive and specific manner. The novel method infers cell death in specific tissue from the methylation patterns of circulating DNA that is released by dying cells.

Cell death is a central feature of human biology in health and disease. It can signify the early stages of pathology; such as a developing tumor or the beginning of an autoimmune or neurodegenerative disease, mark disease progression, reflects the success of identify unintended toxic effects of treatment and more. However, to date, it is not possible to measure cell death in specific human tissues noninvasively.

An international team of scientists led by those at the Hebrew University-Hadassah Medical School (Jerusalem, Israel) developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cell free DNA (cfDNA). They interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. They isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, polymerase chain reaction (PCR)-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest.

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 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. This proof-of-concept study demonstrated that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.

Ruth Shemer, PhD, a DNA methylation expert and one of the lead authors of the study, said, “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.” The study was published on March 14, 2016, in the journal Proceedings of National Academy of Sciences of the United States of America (PNAS).

Related Links:

Hebrew University-Hadassah Medical School


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