超稀有肉瘤（URS）是一组孤儿疾病，年发病率≤每100万人。本研究旨在评估URS中临床可行的基因改变。使用cBioPortal从GENIE数据库中提取数据。利用OncoKB评估突变的临床可行性。从临床测序数据中推断出肿瘤突变负荷（TMB）。软组织（ST）URS占软组织肉瘤病例的23.5％，骨URS占骨肉瘤病例的16.5％。所有四组中最常见的突变基因是TP53。最常见的融合涉及EWSR1。最常见的拷贝数变异包括CDKN2A和CDKN2B的缺失以及MDM2和CDK4的扩增。所有四类肉瘤中的TMB通常较低，尽管具有相当大的异质性，其中23.5％的软组织URS和0.55％的骨URS具有高TMB。我们发现在软组织URS中有10.0％的一级改变（FDA认可的预测对FDA批准药物反应的生物标记物），相比之下软组织非URS中为7.1％，骨URS为1.1 ，骨非URS为4.5％。在软组织URS中发现了27.8％的一至三级改变（也包括具有标准护理药物或临床证据支持的改变），软组织非URS为25.2％，骨URS为20.9％，骨非URS为17.4％。临床可行的基因改变在URS的重要比例中可见。对于先进的URS进行临床测序具有指导相当一部分URS患者治疗的潜力。

Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤ 1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.Data were extracted from the GENIE database using cBioPortal. OncoKB was used to assess for clinical actionability of mutations. Tumor mutational burden (TMB) was inferred from clinical sequencing data.Soft Tissue (ST) URS made up 23.5% of ST sarcoma cases, and bone URS made up 16.5% of bone sarcoma cases. The most commonly mutated gene in all four groups was TP53. The most common fusions involved EWSR1. The most common copy number variations included deletions of CDKN2A and CDKN2B and amplifications of MDM2 and CDK4. TMB was generally low across all four categories of sarcoma, though there was considerable heterogeneity, with 3.8% of ST URS and 0.55% of bone URS having high TMB. We find Level 1 alterations (FDA-recognized biomarker predictive of response to an FDA-approved drug) in 10.0% of ST URS compared to 7.1% of ST non-URS, 1.1% of bone URS, and 4.5% of bone non-URS. Level 1-3 alterations (also include alterations for which there are standard-of-care drugs or clinical evidence supporting a drug) were seen in 27.8 % of ST URS, 25.2% of ST non-URS, 20.9% of bone URS, and 17.4% of bone non-URS.Clinically actionable genomic alterations are seen in a substantial fraction of URS. Clinical sequencing in advanced URS has the potential to guide the treatment of a significant portion of URS patients.