Peroz Morgane, Mananet Hugo, Roussot Nicolas, Kaderbhai Courèche Guillaume, Derangère Valentin, Truntzer Caroline, Ghiringhelli François
Platform of Transfer in Biological Oncology, Georges-Francois Leclerc Cancer Center-UNICANCER, 21000 Dijon, France.
Unité de Formation et de Recherche des Sciences de Santé, University of Burgundy-Franche-Comté, 21000 Dijon, France.
Cancers (Basel). 2024 Sep 9;16(17):3115. doi: 10.3390/cancers16173115.
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. This study investigates the clinical interest of whole exome sequencing (WES) for analyzing somatic mutational signatures in patients with advanced or metastatic NSCLC treated with the current standard of care.
Exome sequencing data and clinical characteristics from 132 patients with advanced or metastatic NSCLC were analyzed. Somatic mutational signatures including single base substitutions (SBSs), double base substitutions (DBSs), and copy number signatures were evaluated. Structural variations including tumor mutational burden (TMB), the number of neoantigens, TCR clonality, homologous recombination deficiency (HRD), copy number alterations (CNAs), and microsatellite instability (MSI) score were determined. The association between these genomic features, NSCLC subtypes, and patient outcomes (progression-free and overall survival) was evaluated.
Exome sequencing offers valuable insights into somatic mutational signatures in NSCLC. This study identified specific signatures associated with a poor response to immune checkpoint inhibitor (ICI) therapy and chemotherapy, potentially aiding treatment selection and identifying patients unlikely to benefit from these approaches.
非小细胞肺癌（NSCLC）仍然是癌症相关死亡的主要原因。本研究探讨了全外显子组测序（WES）在分析接受当前标准治疗的晚期或转移性NSCLC患者体细胞突变特征方面的临床价值。
分析了132例晚期或转移性NSCLC患者的外显子组测序数据和临床特征。评估了体细胞突变特征，包括单碱基替换（SBSs）、双碱基替换（DBSs）和拷贝数特征。确定了结构变异，包括肿瘤突变负荷（TMB）、新抗原数量、TCR克隆性、同源重组缺陷（HRD）、拷贝数改变（CNAs）和微卫星不稳定性（MSI）评分。评估了这些基因组特征、NSCLC亚型与患者预后（无进展生存期和总生存期）之间的关联。
外显子组测序为NSCLC的体细胞突变特征提供了有价值的见解。本研究确定了与免疫检查点抑制剂（ICI）治疗和化疗反应不佳相关的特定特征，可能有助于治疗选择并识别不太可能从这些方法中获益的患者。
