WCLC 2025 - Posters & ePosters-EP.06.46 Frequent Co-Existence of RBM10 Mutation in Patients With Non-Squamous Nsclcs Harboring EGFR Point Mutations

EP.06.46 Frequent Co-Existence of RBM10 Mutation in Patients With Non-Squamous Nsclcs Harboring EGFR Point Mutations

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This study investigated the frequency and co-occurrence of RBM10 mutations in Japanese patients with non-squamous non-small cell lung cancers (NSCLCs), particularly those harboring EGFR point mutations. RBM10 (located on Xp11.3) is an RNA binding motif protein previously implicated in lung cancer biology and TKI therapy tolerance. Using next-generation sequencing (NGS) on 190 surgically resected NSCLC samples from Kindai University between 2022 and 2024, researchers analyzed mutations in RBM10, EGFR, KRAS, TP53, and MDM2.<br /><br />Key findings include:<br /><br />- RBM10 inactivating mutations (nonsense or frameshift) were detected in 11% of non-squamous NSCLC patients but absent in squamous cell carcinoma cases.<br /><br />- RBM10 mutations occurred more frequently in tumors with driver mutations: 21% in EGFR-mutated and 12% in KRAS-mutated cases versus 2% in EGFR/KRAS wild-type tumors. One patient with RBM10 mutation had a MET exon 14 skipping mutation.<br /><br />- Among EGFR-mutated NSCLCs, RBM10 co-mutations were more common in patients with the L858R mutation (26%) and uncommon EGFR mutations (38%) compared to those with exon 19 deletions (9%).<br /><br />- MDM2 amplification was also more prevalent in EGFR-mutated tumors, especially with L858R (17%) and uncommon mutations (18%), versus exon 19 deletion (5%).<br /><br />- TP53 mutations, MDM2 amplifications, and RBM10 mutations tended to be mutually exclusive with distinct patterns between EGFR-mutated and EGFR wild-type non-squamous NSCLCs.<br /><br />These results suggest that RBM10 mutation frequently coexists with specific EGFR mutations in non-squamous NSCLC, especially L858R and uncommon variants, and highlight the complex mutation landscape influencing tumor biology and possibly therapeutic responses. Further research is needed to clarify the clinical implications of RBM10 alterations regarding EGFR-TKI tolerance and NSCLC treatment personalization.

Asset Subtitle

Kenichi Suda

Meta Tag

Speaker Kenichi Suda

Topic Pathology and Biomarkers

Keywords

RBM10 mutations

non-squamous NSCLC

EGFR mutations

L858R mutation

uncommon EGFR mutations

KRAS mutations

TP53 mutations

MDM2 amplification

next-generation sequencing

lung cancer genetics