Abstract
Background: Bone and soft-tissue sarcomas represent 13% of all paediatric 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 centre. Results: Samples of 70 paediatric sarcomas were processed for histopathological analysis, reverse transcriptase polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) with a consensus gene panel. Pathogenic alterations were reported and, if existing, targeted recommendations were translated to the clinic. Seventy paediatric patients with sarcomas from 10 centres 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. Combining all biological studies, 18 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: Paediatric sarcomas have a different genomic landscape when compared to adult cohorts. Incorporating NGS targets into paediatric sarcomas’ therapy is feasible and allows personalized treatments with clinical benefit in the relapse setting.
Highlights
Paediatric sarcomas account for over 20% of all paediatric solid malignant cancers and represent 13% of all paediatric malignancies [1]
Most paediatric sarcomas are included in the second group as they are mostly characterized by chromosomal translocations that result in hybrid genes acting as drivers that are critical for sarcoma-genesis [3]
A total of 70 paediatric and adolescent patients with soft tissue sarcomas (STS) and bone sarcomas (BS) from 10 Spanish cooperating sites were included in a 5-year period from February 2015 to March 2020
Summary
Paediatric sarcomas account for over 20% of all paediatric solid malignant cancers and represent 13% of all paediatric malignancies [1] They contribute substantially to cancer-related mortality and morbidity. With more than 70 histologic subtypes, sarcomas can arise from a primitive mesenchymal cell from almost every tissue in the human body and are classified into two main groups: soft tissue sarcomas (STS) and bone sarcomas (BS). Each subtype has a different phenotype and genetic profile, they are classified into two molecular groups: a genetically complex group with a high mutational burden and complex karyotype, and a genetically simple group containing a single and disease-specific translocation, amplification or mutation with a silent genomic background [2]. Most paediatric sarcomas are included in the second group as they are mostly characterized by chromosomal translocations that result in hybrid genes acting as drivers that are critical for sarcoma-genesis [3]
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