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Updated: Sep 22, 2025
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Molecular landscape and therapeutic alterations in Asian soft-tissue sarcoma patients
Meifu Gan1, Chen Zhang2, Liqing Qiu3
1Department of Pathology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.
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.
Insights
Genomic alterations in soft-tissue sarcoma (STS) reveal that 54% of Chinese patients may benefit from targeted therapies, offering new avenues for precision medicine and potential immunotherapy combinations.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Soft-tissue sarcoma (STS) is a rare malignant tumor with diverse histologic subtypes and significant genomic variability.
- Prognosis in STS is influenced by genomic differences, even within the same subtype.
- Current targeted therapy research for STS is primarily in preclinical and early-phase trials.
Purpose of the Study:
- To investigate genomic alterations (GAs) in Chinese STS patients.
- To identify therapeutic GAs and potential targeted therapy strategies.
- To analyze biomarkers for immunotherapy in STS.
Main Methods:
- Targeted sequencing of 425 genes in 351 Chinese STS patients.
- Bioinformatics analysis of mutations, copy-number variations, and gene fusions.
- Examination of OncoKB therapeutic GAs and biomarkers (TMB, MSI, HRD) for targeted therapy potential.
Main Results:
- Identified 2743 GAs in 330 genes, with TP53, MCL1, and MDM2 being frequently altered.
- Therapeutic GAs were found in 43% of patients across 23 genes.
- 54% of patients showed potential for targeted therapy response, with variations observed between leiomyosarcoma and liposarcoma.
Conclusions:
- This study highlights the potential efficacy of targeted therapy for a significant proportion of STS patients.
- Findings provide insights for developing novel precision therapies for STS.
- Further research into combining targeted therapy with immunotherapy is warranted.
