Abstract 141P
Background
Soft tissue sarcomas are a heterogeneous group of malignant tumours, accounting for the fifth most common paediatric cancer. Next-generation sequencing-based (NGS) comprehensive genomic profiling (CGP) of paediatric soft tissue sarcomas tumours associated with a poor prognosis can identify actionable biomarkers and determine prognostic and therapeutic stratification of patient management.
Methods
Diagnostic samples of 20 patients diagnosed with various paediatric sarcomas were investigated using a CGP assay (Illumina TruSight Oncology 500). The identified single nucleotide variants, small insertions or deletions, copy number alterations, gene fusions, microsatellite stability status, and the tumour mutation burden were analysed. Using Clinical insight (Qiagen) and PierianDx (Pierian) software, actionable variants were determined.
Results
Our study revealed potentially actionable alterations for therapeutic intervention in 75% of cases (15/20). Novel variants were detected in several tumour entities which have not previously been published. All cases were characterised by low tumour mutation burden, with none of the cases characterised by microsatellite instability. The targetable gene fusions included three NTRK fusions, TFG-ROS1, ROS1-GIT2 and EML4-ALK fusions. The most frequent copy number alterations affected the CDK4, ALK and FGFR1 genes, identified in 28.6% (4/20), 14.3% (2/14) and 14.3% (2/14) of the cases, respectively. Single nucleotide variants were detected in 7 genes, including ALK, CHEK2, ESR1, FANCL, MET, NBN and NRAS, across six cases. Based on the NGS results, targeted therapy was prescribed in 5 cases (tazemetostat in epithelioid sarcoma, entrectinib in inflammatory myofibroblastic tumour and infantile fibrosarcoma, larotrectinib in angiosarcoma and infantile fibrosarcoma). At least partial remission was achieved in all patients receiving targeted therapies.
Conclusions
In our study, routine application of the TSO500 CPG assay led to administration of targeted therapies in 25% of the patients with at least partial clinical response in this patient cohort.
Legal entity responsible for the study
C. Bödör and M. Csóka.
Funding
EU Horizon 2020 - 739593, TKP2021-EGA-24, TKP2021-NVA-15, EFOP-3.6.3-VEKOP-16-2017-00009 grants.
Disclosure
All authors have declared no conflicts of interest.