Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma

• DOI: 10.1038/s41467-022-30496-0
• Publication Date: 2022-06-15T10:03:06Z
• Authors: Mrinal M. Gounder; Narasimhan P. Agaram; Sally E. Trabucco; Victoria Robinson; Richard A. Ferraro; Sherri Z. Millis; Anita Krishnan; Jessica Lee; Steven Attia; Wassim Abida; Alexander Drilon; Ping Chi; Sandra P. D’ Angelo; Mark A. Dickson; Mary Lou Keohan; Ciara M. Kelly; Mark Agulnik; Sant P. Chawla; Edwin Choy; Rashmi Chugh; Christian F. Meyer; Parvathi A. Myer; Jessica L. Moore; Ross A. Okimoto; Raphael E. Pollock; Vinod Ravi; Arun S. Singh; Neeta Somaiah; Andrew J. Wagner; John H. Healey; Garrett M. Frampton; Jeffrey M. Venstrom; Jeffrey S. Ross; Marc Ladanyi; Samuel Singer; Murray F. Brennan; Gary K. Schwartz; Alexander J. Lazar; David M. Thomas; Robert G. Maki; William D. Tap; Siraj M. Ali; Dexter X. Jin
• Keywords: Microsatellite Instability

Abstract There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome challenge by providing insight into sarcomas’ molecular drivers. Through targeted panel sequencing 7494 sarcomas representing 44 histologies, we identify highly recurrent type-specific alterations that aid in diagnosis treatment decisions. Sequencing lead to refinement or reassignment 10.5% diagnoses. Nearly one-third patients (31.7%) harbor potentially actionable alterations, including a significant proportion (2.6%) with kinase gene rearrangements; 3.9% have tumor mutational burden ≥10 mut/Mb. We describe low frequencies microsatellite instability (<0.3%) high degree genome-wide loss heterozygosity (15%) across which not readily explained homologous recombination deficiency (observed 2.5% cases). In clinically annotated subset 118 patients, validate genetic events as therapeutic targets. Collectively, our findings reveal landscape human may inform future improve clinical outcomes rare