A powerful next-generation genome-sequencing test developed at Weill Cornell Medicine can detect mutations that guide precision cancer treatment with over 95 percent accuracy, according to new research. The scientists say their findings, published July 20 in NPJ Genomic Medicine, validate the test, called Weill Cornell Medicine EXaCT-1, and demonstrate its feasibility in a clinical setting.
Developed by Weill Cornell Medicine's Englander Institute for Precision Medicine, EXaCT-1 scans 21,000 genes to detect genetic mutations that drive cancer. The precision medicine team can use this information to search for new treatment options and clinical trials that may target patients' diseases.
"We had to demonstrate that we can do genomic testing reliably and reproducibly and that we have procedures in place that are robust and compatible with clinical testing," said co-senior author Dr. Olivier Elemento, head of the Englander Institute's computational biology group, an associate professor of physiology and biophysics, and associate director of the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine at Weill Cornell Medicine.
In order to do so, researchers tested their EXaCT-1 algorithm, based on a type of test known as whole exome sequencing, on 57 tumors for any mutation in five genes. "We worked hard to show that the test is reliable and can find mutations that exist while also not falsely find mutations that don't exist," Dr. Elemento said.
Last fall, EXaCT-1 became the first whole exome test to be approved by the New York State Department of Health for oncology testing. "That was no easy feat. The rigorous nature of the development, testing and validation makes it a challenge for most groups to get approval, but we were able to do so successfully," said co-senior author Dr. Mark Rubin, director of the Englander Institute and the Homer T. Hirst III Professor of Oncology in Pathology at Weill Cornell Medicine, and director of the precision medicine program at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.
Dr. Elemento's team developed a suite of analytic tools that analyzes the data, detects mutations, generates a physical report for physicians to review with their advanced cancer patients and stores the report automatically within the electronic health record. The entire process takes about three weeks on average, but the researchers have shown that it's feasible to perform the test in just six days.
The test has identified expected mutations, or those associated with a specific treatment protocol, as well as potentially relevant mutations in 82 percent of cases involving 337 patients. And for cases where the biological or clinical significance of mutations found is unknown, Dr. Rubin said researchers are taking them to the lab to further examine them.
While EXaCT-1 is primarily an oncology test, researchers can also use it to determine how responsive a patient would be to immunotherapy or to obtain information about a patient's inherited genome, known as the germline. "It has a number of advantages moving forward," Dr. Rubin said.