Subtype-Specific Patterns of Tumor Purity and Mutation Load Suggest Treatment Implications: A Cross-Sectional Analysis of 7494 Soft Tissue and Bone Sarcomas (MSK Cohort).

Objectives: Sarcomas are complex mesenchymal malignancies whose molecular characteristics can significantly influence treatment strategies. This study aimed to investigate the relationship between tumor purity, mutation load, and clinical characteristics across sarcoma subtypes, focusing on potential implications for therapeutic stratification.

Methods: This study analyzed the molecular characteristics of 7494 sarcoma cases from the Soft Tissue and Bone Sarcoma (MSK, Nat Commun 2022) data set using available case analysis. Correlations between tumor purity, mutation load, age, and sex were analyzed using nonparametric methods, with subtype-specific analyses conducted using Kruskal-Wallis tests and Bonferroni-corrected post hoc comparisons. A comprehensive analysis of mutation patterns was performed using microsatellite instability (MSI) status.

Results: Significant correlations between mutation load and tumor purity (ρ=0.320, P <0.001) were identified, with marked heterogeneity across subtypes. Tumor purity ranged from 20.0% in brain sarcomas to 78.5% in dermatofibrosarcoma protuberans. Age-related molecular changes were observed in brain (ρ=0.711, P =0.006) and skin sarcomas (ρ=0.450, P =0.006), suggesting distinct evolutionary patterns. A subset of hypermutated, microsatellite stable cases (0.15%) with mutation loads exceeding 100 mutations/mb were identified, suggesting alternative mechanisms of genomic instability. MSI-high status was rare (0.24%) but associated with higher mutation loads (median: 25.84 vs. 2.42, P <0.001), particularly in uterine sarcomas (0.7% prevalence).

Conclusions: The identification of distinct molecular patterns across sarcoma subtypes challenge existing morphology-based classification systems and may hold implications for therapeutic stratification. These findings may help inform future immunotherapeutic and molecular-guided approaches to treatment in sarcoma patients, particularly for elderly patients with brain sarcomas or females with uterine sarcomas.