Next-Generation Sequencing-based Genomic Profiling of Advanced Soft Tissue and Bone Sarcomas

Yasemin Gündoğdu¹Elif Şenocak Taşçı²Leyla Özer¹Can Boynukara¹Recep Çeçen³Arda Ulaş Mutlu¹İbrahim Yıldız^1*

• ¹Acibadem University, Istanbul, Türkiye
• ²İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Istanbul, Türkiye
• ³Department of Internal Medicine, Istanbul University Cerrahpaşa Faculty of Medicine, Istanbul, Türkiye

Background: Sarcomas are rare mesenchymal tumors classified into soft tissue (STS) and bone sarcomas. Despite advances in treatment, the 5-year survival rate for metastatic disease remains low. There is still limited evidence regarding the use of next-generation sequencing (NGS). Aim: To identify targetable genomic alterations that may play a crucial role in sarcoma treatment where therapeutic options are limited. Study design: Methods: We conducted a retrospective; multicenter analysis of 81 patients diagnosed with STS and bone sarcomas who underwent NGS at Acıbadem Health Group Hospitals to investigate their mutation profiles and explore potential targeted therapies. Results: Genomic profiling using four different NGS kits identified a total of 223 genomic alterations across the cohort. Genomic alterations were detectable in 90.1% of patients, with the most common types being copy number amplifications (26.9%) and deletions (24.7%). In addition, actionable mutations were identified in 22.2% of patients, rendering them eligible for FDA-approved targeted therapies. The most common alterations were found in TP53 (38%), RB1 (22%), and CDKN2A (14%) genes. Among the 79 patients with available microsatellite status data, all were microsatellite stable. Conclusion: The high proportion of patients eligible for targeted therapies identified underscores the critical need to integrate NGS-derived genetic insights into clinical practice to improve survival rates and treatment outcomes through more tailored therapeutic approaches for each individual. NGS also led to a reclassification of diagnosis in four patients, demonstrating its utility not only in therapeutic decision-making but also as a powerful diagnostic tool.