Ciccarone Francesca, Bruno Matteo, De Paolis Elisa, Piermattei Alessia, De Bonis Maria, Lorusso Domenica, Zannoni Gian Franco, Normanno Nicola, Minucci Angelo, Scambia Giovanni, Ferrandina Gabriella
UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy.
Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Cancers (Basel). 2022 Apr 12;14(8):1934. doi: 10.3390/cancers14081934.
Uterine leiomyosarcomas (uLMS) is a very rare disease, and patients experience a dismal prognosis even when treated with chemotherapy. Therefore, a more in-depth molecular characterization of this disease could provide suitable data for the identification of potential target-based drugs. This retrospective, single institutional study aimed to define the frequencies of gene alterations in uLMS, especially regarding the somatic mutations of and Homologous Recombination Repair (HRR) genes, and the impact of molecular alterations on clinical outcomes. The 16-genes Next-Generation Sequencing (NGS) panel, Homologous Recombination Solution TM (HRS, Sophia Genetics, Saint Sulpice, Switzerland), was used for the molecular evaluation of samples. The majority of patients (66/105, 63%) carried at least one sequence alteration, with a prevalence of involvement followed by , , and . Patients with gene alterations experienced a significantly worse prognosis for progression free survival (PFS) and overall survival (OS) versus wild-type patients. Given the number of patients with the mutation (N = 12), we included them in the HRR patient group; there was no difference in clinical outcomes with HRR versus non-HRR. The Cox's multivariate analysis showed that stage and gene alterations resulted in a significantly worse OS. The integration of gene networking data, such as tumor mutation burdens and cancer driver gene identification, could show a clearer discrimination of gene distribution patterns, and lead to the implementation of therapeutic targets.
子宫平滑肌肉瘤（uLMS）是一种非常罕见的疾病，即使接受化疗，患者的预后也很差。因此，对这种疾病进行更深入的分子特征分析可为识别潜在的靶向药物提供合适的数据。这项回顾性单机构研究旨在确定uLMS中基因改变的频率，特别是关于[具体基因]和同源重组修复（HRR）基因的体细胞突变，以及分子改变对临床结果的影响。使用16基因下一代测序（NGS）面板Homologous Recombination Solution TM（HRS，Sophia Genetics，瑞士圣叙尔皮斯）对样本进行分子评估。大多数患者（66/105，63%）至少携带一种序列改变，[具体基因]受累的患病率最高，其次是[其他基因]、[其他基因]和[其他基因]。与野生型患者相比，发生[具体基因]改变的患者在无进展生存期（PFS）和总生存期（OS）方面的预后明显更差。鉴于发生[具体突变基因]突变的患者数量（N = 12），我们将他们纳入HRR患者组；HRR组与非HRR组的临床结果没有差异。Cox多变量分析表明，分期和[具体基因]改变导致OS明显更差。整合基因网络数据，如肿瘤突变负担和癌症驱动基因识别，可能会更清楚地辨别基因分布模式，并促成治疗靶点的实施。
