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Johns Hopkins scientists develop personalized blood tests for cancer using whole genome sequencing
Date:2/18/2010

ta of each patient. To find DNA rearrangements, the team first identified regions where the number of DNA copies was more or less than anticipated and where sections of different chromosomes fused together. These regions were further analyzed to identify DNA sequences displaying incorrect ordering, orientation, or spacing. A range of four to 15 rearrangements were found in each of the six samples.

After investigators identified DNA rearrangements in patients' tumor samples, they looked for the same changes in DNA shed from tumors into the patients' blood. Using blood samples from two of the colorectal cancer patients, they amplified DNA found in the blood and determined that these tests were sensitive enough to detect rearranged tumor DNA in these samples.

Results from such blood tests, they say, could help clinicians detect cancer or its recurrence and inform them on how a patient is responding to cancer therapies. In one colon cancer patient's example, the scientists found a section of chromosome four fused to a section of chromosome eight. "We developed a biomarker that could span this rearrangement and used a blood test to evaluate biomarker levels as the patient received a variety of cancer therapies," says Rebecca Leary, a graduate student at the Johns Hopkins Kimmel Cancer Center.

After an initial surgery, the patient's biomarker levels dropped due to the removal of the majority of the tumor. The biomarker levels rose again, indicating that additional cancer remained in the patient's body. After chemotherapy and a second surgery, levels of the biomarker dropped substantially, but still showed a small but measurable level of the biomarker. This was consistent with a small metastatic lesion that remained in the patient's liver.

The investigators envision that PARE-based biomarkers could also be used to determine whether cancer cells are present in surgical margins or lymph node tissue removed during surgery and possibly for diagnosing e
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Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

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