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Study Aims to Use Sequencing to ID Patient-Specific Biomarkers in Glioblastoma, Monitor Therapy

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By Monica Heger

This story was originally published on April 21.

Testing a hypothesis that specific rearrangements found in tumor DNA can be used as biomarkers, researchers from the University of Cincinnati are sequencing tumor and matched normal DNA from 10 glioblastoma patients, looking for structural variations that can be used as biomarkers.

The goal is to identify patient-specific rearrangements in the primary tumor, and then use PCR to check for the presence of that rearrangement in the patient's blood during treatment in order to determine tumor progression and monitor therapy response.

"The hope is that we'd be able to follow the tumor in a more sensitive way than methods currently available," such as using MRI scans, said Peter Stambrook, a professor of molecular genetics at the University of Cincinnati and a lead researcher on the project.

Sequencing for the project will be done at the Albert Einstein College of Medicine in New York on the Illumina Genome Analyzer, and the project will last about one year. It is being funded through a $50,000 grant from the Mayfield Education and Research Fund, and the University of Cincinnati Brain Tumor Center is providing the samples.

Stambrook said that the team would likely start with exome sequencing, but may move into whole-genome sequencing if funding allows.

After sequencing the tumor and germline DNA, the team will then look for rearrangements unique to the tumor genome that could be used to detect the presence of circulating tumor DNA, the amount of which would help inform tumor progression and therapy response.

Stambrook said that the team expects to choose around two rearrangements per patient, and that the rearrangements would likely differ from patient to patient. He said that the team is particularly interested in identifying translocations that occur between chromosomes as well as large deletions because they would be the easiest to detect in the patient's blood using PCR.

"This is really individualized medicine because each tumor will have a different rearrangement or set of rearrangements," he said.

The team will then follow up about every two weeks as the 10 patients undergo standard treatment, by drawing blood and then looking for the presence of the chosen biomarkers using PCR.

"By drawing blood after surgery, radiation treatment, or chemotherapy, you can follow the progression of tumors by the appearance of tumor-specific rearrangements," Stambrook said.

There is already some evidence that the approach could be successful. Last year, a group from Johns Hopkins University used a similar method to identify patient-specific rearrangements in breast and colon cancer (IS 2/23/2010).

The Hopkins team sequenced two tumor/normal pairs of breast and colon cancer and two additional colon tumors without matched normals. In the proof-of-principle study, published last year in Science Translational Medicine, the team was able to identify the patient-specific rearrangements in mixtures of DNA. Additionally, they identified the biomarker in a real patient before and after surgery, noting that after surgery the biomarker was present in much lower concentration.

If Stambrook's team is successful, the hope is that the technique could be used to monitor disease progression and response to therapy on any cancer patient, particularly those with solid tumors, which tend to contain a large number of rearrangements.

"The earlier you detect something, the more likely you will be able to get a response or treat [the cancer] in a way that will elicit a favorable response," said Stambrook.


Have topics you'd like to see covered by Clinical Sequencing News? Contact the editor at mheger [at] genomeweb [.] com.

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