Personalized blood tests for cancer have been developed by Johns Hopkins Kimmel Cancer Center scientists by using whole genome sequencing.
Boffins have used data from the whole genome sequencing of cancer patients to develop individualized blood tests they believe can help physicians tailor patients' treatments. The genome-based blood tests, believed to be the first of their kind, may be used to monitor tumor levels after therapy and determine cancer recurrence.
Advertisement"We believe this is the first application of newer generations of whole-genome sequencing that could be clinically useful for cancer patients," says Victor Velculescu, M.D., Ph.D., associate professor of oncology and co-director of the cancer biology program at Johns Hopkins. "Using this approach, we can develop biomarkers for potentially any ancer patient."
In a report on the work, published in the February 24 issue of Science Translational Medicine, the scientists scanned patients' genomes for alterations that, they say, most researchers have not been looking for - rearrangements of large chunks of DNA rather than changes in a single DNA letter among billions of others. They call their new approach Personalized Analysis of Rearranged Ends (PARE).
"In sequencing individuals' genomes in the past, we focused on single-letter changes, but in this study, we looked for the swapping of entire sections of the tumor genome," says Bert Vogelstein, M.D., Clayton Professor of Oncology, co-director of the Ludwig Institute at Johns Hopkins, and Investigator in the Howard Hughes Medical Institute.
These alterations, like the reordering of chapters of a book, are easier to identify and detect in the blood than single-letter changes."
Such DNA rearrangements are widely known to occur exclusively in cancer cells, not normal ones, making them ideal biomarkers for cancer.
Using six sets of cancerous and normal tissue samples taken from four colorectal and two breast cancer patients, the Johns Hopkins team used next-generation sequencing methods to catalogue the genome sequence data 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.
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