Complete genomic sequencing is essential to capitalize on precision medicine for pediatric cancer care

Researchers at St. Jude Children’s Research Hospital have demonstrated that complete genomic sequencing of all pediatric cancer patients is feasible and essential to capitalize on the lifesaving potential of precision medicine. The results of the St. Jude Genomes for Kids study are published online today in the journal Discovery of cancer.

Whole genome and whole exome sequencing of germline DNA was offered to the 309 patients who participated in the study. Whole genome, whole exome, and tumor DNA RNA sequencing was performed for the 253 patients for whom adequate tumor samples were available.

Overall, 86% of patients had at least one clinically significant variation in tumor or germ DNA. These included variants related to diagnosis, prognosis, therapy, or predisposition to cancer. Researchers estimated that one in five patients had clinically relevant mutations that would not have been detected using standard 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,” said Jinghui Zhang, Ph. D., chairman of the computational biology department of St. Jude and co-corresponding author of the study.

Each tumor is unique. Each patient is unique.

Complete clinical sequencing which includes whole genome, whole exome and RNA sequencing is not widely available. But as the technology becomes cheaper and accessible to more patients, researchers said full sequencing will become an important addition to pediatric cancer care.

We want to change the way of thinking on the ground. We have shown the potential to use genomic data at the patient level. Even in common pediatric cancers, every tumor is unique, every patient is unique. “

David Wheeler, Ph.D, study co-author and team leader, St. Jude Precision Genomics, St. Jude Children’s Research Hospital

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

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

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

Findings and additional details

Genomes for Kids recruited patients between August 2015 and March 2017.

Eighteen percent of the patients carried germline variations in one of 156 known cancer predisposition genes.

Almost two-thirds of the identified germline variations would not have been detected based on current screening guidelines.

Next steps

Genomes for Kids helped launch the hospital’s clinical genomics program, which has enrolled approximately 2,700 cancer patients to date.

Meanwhile, the data generated by the Genomes for Kids study is available free to the international research community. By sharing data, St. Jude aims to accelerate progress in understanding and treating pediatric cancer. The data is available in St. Jude Cloud.

“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 will not need to collect complete genomic data on all patients.”