Next-Generation Sequencing Identifies Potential Actionable Targets In Pediatric Sarcomas

BACKGROUND Pediatric bone and soft-tissue sarcomas represent 13% of all pediatric malignancies. International contributions to introduce next-generation sequencing (NGS) approaches into clinical application are currently developing. We present the results from the Precision Medicine program for children with sarcomas at a reference center. RESULTS Samples of 70 pediatric sarcomas were processed for histopathological analysis, RT-PCR and NGS with a consensus gene panel. Pathogenic alterations were reported and if existing, targeted recommendations were translated to the clinic. Seventy pediatric patients with sarcomas from 10 centers were studied. Median age was 11.5 years (range 1-18). Twenty-two (31%) had at least one pathogenic alteration by NGS. Thirty pathogenic mutations in 18 different genes were detected amongst the 22 patients. The most frequent alterations were found in TP53 , followed by FGFR4 and CTNNB1. Eighteen actionable variants were detected and six patients received targeted treatment observing a disease control rate of 78%. Extrapolating the results to the whole cohort, 23% of the patients would obtain clinical benefit from this approach. CONCLUSIONS Pediatric sarcomas have a different genomic landscape when compared to adult cohorts. Incorporating NGS targets into pediatric sarcomas’ therapy is feasible and allows personalized treatments with clinical benefit in the relapse setting.