A study of 124 advanced breast, lung and prostate cancer patients demonstrated that a new, high-intensity genomic sequencing approach can detect circulating tumor DNA at a high rate.
In the study, which was presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, 89 percent of the patients had at least one genetic change detected in the tumor that was also detected in the blood.
Also, 627 genetic changes found in tumor samples were also found in blood samples using this new approach.
“Our findings show that high-intensity circulating tumor DNA sequencing is possible and may provide invaluable information for clinical decision-making, potentially without any need for tumor tissue samples,” lead study author Dr. Pedram Razavi, Ph.D., a medical oncologist and instructor in medicine at Memorial Sloan Kettering Cancer Center, said in a statement. “This study is also an important step in the process of developing blood tests for early detection of cancer.”
Razavi said the approach is not intended to be commercially available to patients and the researchers will now use the technology to potentially develop a blood test for early cancer detection.
The researchers used a combination of breadth and depth by scanning a very broad area of the genome—508 genes and more than two million base pairs or letters of the genome—with high accuracy, yielding about 100 times more data than other sequencing approaches.
In liquid biopsies, including commercial tests, only a relatively small portion of the genome are profiled. Those tests are also only used on patients already diagnosed with cancer in order to help monitor the disease or detect actionable alterations that can be matched to available drugs or clinical trials.
The researchers analyzed tumor tissues using MSK-IMPACT—a 410-gene diagnostic test that provides detailed genetic information about a patient’s cancer. They also separated the plasma in blood cells and extracted cell-free DNA from the plasmas and separately sequenced the genome of white blood cells using the high-intensity, 508-gene sequencing assay.
“Finding tumor DNA in the blood is like looking for a needle in a haystack. For every 100 DNA fragments, only one may come from the tumor and the rest may come from normal cells, mainly bone marrow cells,” Razavi said. “Our combined analysis of cell-free DNA and white blood cell DNA allows for identification of tumor DNA with much higher sensitivity, and deep sequencing also helps us find those rare tumor DNA fragments.”
The test detected at least one genetic change in the tumor and the blood in 97 percent of the breast cancer patients, 85 percent of the lung cancer patients and 84 percent of the prostate cancer patients.
“Prior research in the field has primarily focused on using knowledge from tumor tissue sequencing to identify specific changes to look for in circulating tumor DNA,” Razavi said. “This approach allows us to detect, with high confidence, changes in circulating tumor DNA across a large part of the genome without information from tumor tissue.”
Filed Under: Genomics/Proteomics