Comprehensive genomic profiling refines diagnosis and reveals clinically relevant alterations in pediatric Soft...

Pediatric soft tissue sarcomas (STS) are rare malignancies that present significant challenges in diagnosis and treatment. Comprehensive genomic profiling holds promise in addressing these challenges by revealing the molecular drivers of these tumors. In this study, we conducted DNA sequencing on 50 pediatric STS samples, encompassing a diverse range of histologies. Utilizing advanced sequencing technologies and analytical tools, we identified recurrent genetic alterations that may guide diagnostic and therapeutic strategies. The most frequent mutations included alterations in EWSR1-FLI1, TP53, KRAS, and IGF1R. Notably, 34% of patients harbored mutations in the RTK-RAS signaling pathway, and 11 previously unreported gene mutations were identified. Gene amplifications were more common in rhabdomyosarcoma, while gene fusions were predominantly observed in non-rhabdomyosarcoma subtypes, particularly Ewing sarcoma. Our analysis of cooperative mutations revealed four groups of co-occurring genetic alterations, with no evidence of mutually exclusive mutations. Clinically, we observed significant correlations between specific genetic mutations and clinical parameters, such as age at diagnosis and fibrinogen levels, providing insights into potential prognostic factors. These findings offer a detailed genetic landscape of pediatric STS, emphasizing the importance of genomic profiling in improving diagnostic accuracy and identifying new therapeutic targets for this rare cancer.