Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA.
Department of Pathology, City of Hope National Medical Center, Duarte, CA.
Clin Lung Cancer. 2024 Dec;25(8):e411-e419. doi: 10.1016/j.cllc.2024.07.010. Epub 2024 Jul 23.
According to WHO, lung cancer is the leading cause of cancer-related death worldwide, but treatment has advanced in the last decade. The widespread use of Next Generation Sequencing has led to the discovery of several pathogenic mutations including RNA binding motif 10 (RBM10), a part of the spliceosome complex that regulates splicing of pre-mRNA.
Electronic medical records were utilized to create a database of patients (50 patients) seen from 2018-2023 with NSCLC and RBM10 mutations, with appropriate IRB approval. For subgroup analysis, we separated into groups by rapid progression vs stable disease defined as progression-free survival earlier than respective clinical trials.
From the analysis of treatment response the mutated RBM10 population had a median PFS was 6.7 months compared to 13.9 in the wild-type RBM10 population controlled for driver mutations TP53 mutation had a higher representation in the RBM10 mutated rapid progression group than the stable disease group. The ZFHX3 mutation had a higher representation in the RBM10 mutated stable disease group.
RBM10 mutations were associated with aggressive disease with treatment progression faster than median durations of response. RBM10 mutations with concurrent ZFHX3 and EGFR mutations were associated with more stable disease, while concurrent KRAS and TP53 predicted even more aggressive disease.
根据世界卫生组织的数据，肺癌是全球癌症相关死亡的主要原因，但在过去十年中，治疗方法已经取得了进展。下一代测序的广泛应用发现了几种致病性突变，包括 RNA 结合基序 10（RBM10），它是剪接体复合物的一部分，调节前体 mRNA 的剪接。
利用电子病历创建了一个数据库，其中包含 2018 年至 2023 年间患有 NSCLC 和 RBM10 突变的患者（50 名患者）的信息，并获得了适当的 IRB 批准。为了进行亚组分析，我们根据无进展生存期（定义为早于各自临床试验的无进展生存期）将快速进展与稳定疾病的患者分为两组。
从治疗反应分析来看，突变 RBM10 组的中位 PFS 为 6.7 个月，而野生型 RBM10 组为 13.9 个月，在考虑到驱动突变 TP53 突变的情况下，突变 RBM10 快速进展组的 RBM10 突变患者比例高于稳定疾病组。在 RBM10 突变的稳定疾病组中，ZFHX3 突变的比例更高。
RBM10 突变与侵袭性疾病相关，治疗进展速度快于中位反应持续时间。与 ZFHX3 和 EGFR 突变同时存在的 RBM10 突变与更稳定的疾病相关，而同时存在 KRAS 和 TP53 则预示着更具侵袭性的疾病。
