Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients

Background Soft‐tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early‐phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate the genomic alterations (GAs) and the potential of targeted therapy in STS, we analyzed the genomic landscape, the therapeutic GAs, and biomarkers of immunotherapy in Chinese STS patients. Methods Targeted sequencing covering 425 genes was performed, from which we obtained the results of tissue samples from 351 Chinese STS patients of all ages covering different histologic subtypes. Bioinformatics analysis of altered genes with nonsynonymous mutations, copy‐number variations, and gene fusions were performed. OncoKB therapeutic GAs and relevant biomarkers including TMB, MSI, and HRD were further examined for potential targeted therapy. Results In total, 2743 GAs were identified in 330 genes with a median of 6 (1–38) per case. The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. OncoKB defined therapeutic GAs were found in 23 genes in 43% of the patients. In general, 9.4% of the patients had high‐TMB, 2.8% had MSI, and 13.7% had HRD. A significant difference in the percentage of patients with OncoKB therapeutic GAs were observed between the most frequent two subtypes, leiomyosarcoma and liposarcoma. Altogether, 54% of the patients had the potential to respond to a targeted therapy. Conclusion This study indicated the potential efficacy of targeted therapy on many STS patients, and also provided insight for novel precision therapy. The clinical efficacy of combining targeted therapy and immunotherapy can be further investigated. We report an overall landscape of genomic alterations as well as immunotherapy biomarkers in Chinese soft‐tissue sarcoma patients of all ages with different subtypes. we investigated the potential of targeted therapy in soft‐tissue sarcoma showing the proportion of patients with OncoKB defined therapeutic alterations, TMB high, MSI and HRD. This is the first comprehensive genomic landscape of soft‐tissue sarcoma in Asian patients supporting the potential efficacy of targeted therapy and immunotherapy. Our results provide insights for more options of personalized medicine to improve the prognosis for patients with such a rare cancer.