Objective: To understand the genetic variation of soft tissue sarcomas, and to provide a scientific evidence for the individualized treatment. Methods: The somatic mutation and germline mutation of 45 adult soft tissue sarcomas had been detected by high-throughput sequencing technology, the clinical data were also analyzed. Results: A total of 88 gene mutations were detected in 45 samples, including 78 single nucleotide variation (SNV), 13 insertion/deletion (Indel) and 19 copy number variation (CNV). The most common mutant genes are TP53, CDKN2A, MDM2, CDK4, NF1 and PTEN. Among them, the mutation rates of TP53-MDM2/MDM4-CDKN2A pathway, CDKN2A/CDK4/RB1 pathway, and RAS/NF1/PTEN/PI3K pathway were more frequent (32/88, 36%). In terms of immunotherapy biomarkers among 10 samples, the median value of tumor mutation burden was 2.02 muts/Mb (0-4.24 muts/Mb), and all were microsatellite stable. Conclusions: This study analyzes the genetic variation of soft tissue sarcoma, and determines the high-frequency gene mutations and pathways, which may be the potential drug targets. This finding can provide scientific evidences for the personalized treatment of soft tissue sarcoma.
目的： 探讨成人软组织肉瘤的基因变异情况，为软组织肉瘤的个体化治疗提供依据。 方法： 收集45例成人软组织肉瘤标本，利用高通量测序技术(HTS)检测肿瘤组织的体细胞突变和胚系突变的基因变异情况，绘制基因变异图谱，结合患者的临床病理特征进行分析。 结果： 45例软组织肉瘤共检测出88个基因中存在的110个变异信息，包括单核苷酸变异78个，插入或缺失13个，拷贝数变异19个。最常见的突变基因为TP53、CDKN2A、MDM2、CDK4、NF1和PTEN等，其中TP53-MDM2/MDM4-CDKN2A通路、CDKN2A/CDK4/RB1通路以及RAS/NF1/PTEN/PI3K通路变异频率最高(32/88，36.4%)。10例患者进行肿瘤突变负荷(TMB)和微卫星不稳定状态检测，TMB为0～4.24个突变/Mb，中位值为2.02个突变/Mb，10例患者均为微卫星稳定型。 结论： 共检测到88个基因突变，其中TP53-MDM2/MDM4-CDKN2A通路、CDKN2A/CDK4/RB1通路以及RAS/NF1/PTEN/PI3K通路变异频率最高；有高频基因突变的患者存在潜在可用药靶点，有可能为软组织肉瘤的个体化治疗提供依据。.
Keywords: Gene mutation; High-throughput sequencing; Personalized treatment; Soft tissue sarcoma.