Diagnostic Technique Uses Signature Chemical Differences in Leukocyte DNA

The relative abundance of signature chemical differences (methylation) in the leukocyte DNA correlates with specific cancers and other diseases, making the technique potentially valuable not only for research but also for diagnostics and treatment monitoring.

A group of scientists at several institutions including Brown University (Providence, RI, USA) discovered a way to determine that mix of the various types of immune cells called leukocytes from the DNA in archival or fresh blood samples. This potentially provides a practical new technology not only for medical research but also for clinical diagnosis and treatment monitoring of ailments including some cancers.

In another paper published in advance online June 19, 2012, in Cancer Epidemiology, Biomarkers, and Prevention, the scientists describe using their technique to distinguish accurately which blood samples came from patients with head and neck squamous cell carcinoma, ovarian cancer, or bladder cancer. By using methylation to determine the leukocyte populations in each sample, they could predict that the same samples were as much as 10 times more likely to have come from a patient with ovarian cancer than a healthy control patient, six times more likely to be from a head and neck cancer patient than a healthy control, or twice as likely to be from a bladder cancer patient than a control.

“You can simply look at the DNA and discern from the methylation marks the relative abundance of different type of leukocytes,” said Karl Kelsey, professor of pathology and laboratory medicine in the Warren Alpert Medical School of Brown University and a senior author on both papers. “It’s a way to more easily interrogate the immune system of a lot of people.”

The DNA in a blood sample remains present even after cells have died and degraded, and therefore tests based on detecting methylation could help scientists analyze a patient’s blood sample that has either aged or has simply not been kept fresh. This gives the technique advantages over other currently used methods.

The scientists describe the technique and its analytical methods in full mathematical detail in another paper published in May 2012 in BMC Bioinformatics. They also report experiments that included analyses of the leukocyte mix of noncancer conditions such as Down syndrome and obesity.

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