DNA and RNA-Seq Help Reveal Vulnerabilities in Pediatric Cancers

St. Jude Children's Research Hospital investigators have demonstrated that comprehensive genomic sequencing of all pediatric cancer patients is feasible and essential to capitalize on the lifesaving potential of precision medicine. Results from the St. Jude Genomes for Kids study were published in Cancer Discovery.

Whole-genome and whole-exome sequencing of germline DNA were offered to all 309 patients who enrolled in the study. Whole-genome, whole-exome, and RNA sequencing of tumor DNA was carried out 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 germline DNA. Those included variants related to diagnosis, prognosis, therapy, or cancer predisposition. Researchers estimated that 1 in 5 patients had clinically relevant mutations that would have gone undetected 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, co-corresponding author of the study. "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 unsuccessful. In four of the 12 patients, the changes stabilized disease and extended patient lives. Another patient, one with acute myeloid leukemia, went into remission and was cured by blood stem cell transplantation.

"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."