The scientists scanned patients’ genomes for alterations – rearrangements of large chunks of DNA rather than changes in a single DNA letter among billions of others. “In the past, we focused on single-letter changes, but in this study, we looked for the swapping of entire sections of the tumour genome,” says Bert Vogelstein, one of the researchers. "These alterations are easier to identify and detect in the blood." 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 research team used sequencing methods to catalogue the genome sequence data of each patient. To find DNA rearrangements, the team 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 analysed 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 tumour samples, they looked for the same changes in DNA shed from tumours into the patients’ blood. Using blood samples from two of the cancer patients, they amplified DNA found in the blood and determined that these tests were sensitive enough to detect rearranged tumour DNA in these samples.
After an initial surgery, the patient’s biomarker levels dropped due to the removal of the majority of the tumour. 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.
Results from such blood tests could help clinicians detect cancer or its recurrence and inform them on how a patient is responding to a therapy, according to the researchers. They have filed for patents on the technology.
MEDICA.de; Source: Johns Hopkins Medicine