Background/Objectives:Targeted gene sequencing (TGS) for Comprehensive Genomic Profiling (CGP) use in sarcomas has recently increased in clinical practice. We report on TGS real-world data over a period of 3 years (2022–2025) at the IRCCS Istituto Ortopedico Rizzoli, with the aim of identifying potential actionable targets and providing therapeutic indications for advanced sarcoma patients.Methods:We analyzed 22 advanced sarcoma patients by using the VariantPlex Pan Solid Tumor kit panel, including 185 genes. In nine cases, saliva samples for germinal DNA analysis were available. Sequencing was performed on the NextSeq-500 Platform and analyzed with Archer Analysis software. The Cancer Genome Interpreter and OncoKB Database tools were used to find potential actionable targets.Results:We found the most frequent genetic variants, including missense, deletion, duplication, and delins, in the NOTCH4, AR, BARD1, MUC16, and ROS1 genes. Copy Number alterations affected the CDKN2A, CDKN2B, TP53, RHOA, MYC, CCND3, and DDR2 genes mainly in osteosarcoma samples. In four patients, longitudinal analyses of subsequent lesions showed the maintenance of most genomic alterations and enrichment in missense or splice variants in PMS2, SMARCA4, ARID1A, AKT1, BMPR1A, and PTEN, indicating the occurrence of tumor evolution. Germline variants subtraction identified the specific somatic tumor mutations. Advantages and disadvantages of our approach were considered in order to refine the analysis setting and better select possible actionable targets.Conclusions:Early access to genomic analyses, routine germline assessment, and broad gene panels would help in identifying possible targeted drugs with sufficient evidence of activity beneficial to each patient. In the clinical management of advanced sarcoma patients, when analyzing cost-effectiveness and sustainability, the role of the Molecular Tumor Board in the governance of the complexity introduced by mutational oncology should be considered.
背景/目的：近年来，靶向基因测序（TGS）用于肉瘤全面基因组分析（CGP）在临床实践中的应用日益增多。我们报告了IRCCS Istituto Ortopedico Rizzoli机构为期三年（2022–2025年）的TGS真实世界数据，旨在识别潜在的可操作靶点，并为晚期肉瘤患者提供治疗指导。 方法：我们使用包含185个基因的VariantPlex Pan Solid Tumor试剂盒对22例晚期肉瘤患者进行了分析。其中9例患者可获得用于胚系DNA分析的唾液样本。测序在NextSeq-500平台上进行，并使用Archer Analysis软件进行分析。利用Cancer Genome Interpreter和OncoKB数据库工具寻找潜在的可操作靶点。 结果：我们在NOTCH4、AR、BARD1、MUC16和ROS1基因中发现了最常见的遗传变异，包括错义、缺失、重复和插入缺失突变。拷贝数变异主要影响骨肉瘤样本中的CDKN2A、CDKN2B、TP53、RHOA、MYC、CCND3和DDR2基因。在4例患者中，对后续病灶的纵向分析显示，大多数基因组改变得以维持，并且在PMS2、SMARCA4、ARID1A、AKT1、BMPR1A和PTEN基因中错义或剪接变异富集，表明肿瘤进化发生。通过胚系变异减除确定了特定的体细胞肿瘤突变。我们考虑了本方法的优缺点，以优化分析设置并更好地筛选可能的可操作靶点。 结论：早期获取基因组分析、常规胚系评估以及使用广泛的基因panel，将有助于识别对每位患者有益且具有充分活性证据的潜在靶向药物。在晚期肉瘤患者的临床管理中，分析成本效益和可持续性时，应考虑分子肿瘤委员会在管理突变肿瘤学引入的复杂性方面的作用。
肿瘤(癌症)患者之家