RBM10 Mutation as a Potential Negative Prognostic/Predictive Biomarker to Therapy in Non-Small-Cell Lung Cancer.

ABSTRACT

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.