Genomic Sequencing Creates Precision Medicine for Cancer Patients

July 27, 2021 - Researchers at St. Jude Children’s Research Hospital have discovered that comprehensive genomic sequencing of all pediatric cancer patients is achievable and essential in the development of precision medicine.

In the study, 309 patients were offered whole genome and whole exome sequencing of germline DNA. Of those, whole genome, whole exome, and RNA sequencing of tumor DNA were carried out in 253 patients.

According to the data, 86 percent of patients were found to have at least one clinically significant variation in the tumor or germline DNA. This included variations associated with diagnosis, prognosis, therapy, or cancer predisposition. As a result, researchers estimated that 1 in 5 patients had clinically relevant mutations that would have gone unnoticed using typical sequencing methods.

“Some of the most clinically relevant findings were only possible because the study combined whole genome sequencing with whole exome and RNA sequencing,” Jinghui Zhang, PhD, St. Jude Department of Computational Biology chair and co-corresponding author of the study, said in a press release.

Currently, comprehensive clinical sequencing that includes whole genome, whole exome, and RNA sequencing is not readily available. However, when the technology becomes more accessible to patients and less expensive, researchers claim that comprehensive sequencing will be a critical addition to pediatric cancer care.

 “We want to change the thinking in the field,” said David Wheeler, PhD, St. Jude Precision Genomics team director and a co-author of the study. “We showed the potential to use genomic data at the patient level. Even in common pediatric cancers, every tumor is unique, every patient is unique.”

“This study showed the feasibility of identifying tumor vulnerabilities and learning to exploit them to improve patient care,” he said.

Tumor sequencing guided the change in treatment for 12 of the 78 study patients for whom the standard of care was not working. In four of the 12 patients, the treatment changes stabilized the disease and extending the patients’ lives. Another patient with acute myeloid leukemia went into remission and was cured by a blood stem cell transplant.  

“Through the comprehensive genomic testing in this study, we were able to clearly identify tumor variations that could be treated with targeted agents, opening doors for how oncologists manage their patients,” said co-corresponding author Kim Nichols, MD, St. Jude Cancer Predisposition Division director.

“Even the most treatable cancers are not curable in all patients. For example, relapse remains the leading cause of death for the most common childhood cancer, acute lymphoblastic leukemia,” Nichols said. “Being able to understand and predict which patients will respond to treatment and which won’t require collecting comprehensive genomic data on all patients.”