Using data from whole genome sequencing of cancer patients, scientists at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, have developed individual blood tests that may lead to personalized treatments for patients.

The tests are believed to be the first of their kind and may help monitor tumor levels after therapy and determine cancer recurrence. The technique of identifying personalized biomarkers from tumor DNA using next-generation sequencing technology was reported in Science Translational Medicine.1

“We believe this is the first application of newer generations of whole-genome sequencing that could be clinically useful for cancer patients,” says senior author Victor Velculescu, MD, PhD, associate professor of oncology and co-director of the cancer biology program at Johns Hopkins, in a news release. “Using this approach, we can develop biomarkers for potentially any cancer patient.”

The new approach, called Personalized Analysis of Rearranged Ends (PARE), involves scanning patients' genomes for rearrangements of large chunks of DNA rather than changes in a single DNA letter among billions of others. Bert Volgestein, MD, co-director of the Ludwig Institute at Johns Hopkins, describes the new technique as detecting alterations like reordering the chapters of a book versus trying to detect single-letter changes in the blood. Many of these DNA rearrangements are known to be unique to cancer cells, making them excellent tumor biomarkers. As a result, PARE provides a highly accurate and specific way to identify remaining cancer cells after surgery and during therapy, Dr. Vogelstein notes.

The team used 6 sets of cancerous and normal tissue samples from 4 patients with colorectal cancer and 2 patients with breast cancer and then catalogued the genome sequence data of each patient. A range of 4 to 15 rearrangements were found in each of the 6 tumor samples. The researchers then looked for similar DNA changes in patients' blood samples and found that the tests were able to detect rearranged DNA in these samples as well.

In a patient with colon cancer, for example, scientists found a section of chromosome 4 fused to a section of chromosome 8. They developed a biomarker that could span the rearrangement and used a blood test to evaluate biomarker levels throughout the patient's treatment. The biomarkers dropped after initial removal of the tumor, then rose again, showing that more cancer remained. After the patient received chemotherapy and more surgery, the biomarker dropped again.

Although PARE is expensive (about $5000 per patient), costs are expected to drop. (In comparison, computed tomography [CT] scans are about $1500 per scan but are not as able to detect microscopic cancers.) As the technology becomes more affordable, PARE may make a huge impact on how cancer treatments are assessed, the researchers note. The team plans on testing more patient samples and refining their methods to develop a commercial genome-based blood test.


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