Related Experiment Video
Updated: Apr 5, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Frequent RBM10 Comutation and a Mutually Exclusive Relationship With Other TP53 Pathway Aberrations in Early-Stage
Kenichi Suda1, Kazuko Sakai2, Masaoki Ito3
1Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Sakai, Japan; Department of Thoracic Surgery, Izumi City General Hospital, Izumi, Japan.
Background:
RNA-binding motif 10 (RBM10) mutation in non-small-cell lung cancer (NSCLC) is associated with decreased sensitivity to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in vitro and in patients who received osimertinib as neoadjuvant treatment or palliative systemic therapy. The incidence of this mutation in early-stage NSCLC and the relationship with other mutations are unknown.
Materials And Methods:
We analyzed the clinical and genomic data of 190 patients with NSCLC who underwent surgical resection between June 2022 and April 2024. Genomic data were obtained from whole-exome sequencing performed in an ongoing multicenter prospective observational study.
Results:
RBM10 mutation was detected in 17 of 152 patients with nonsquamous NSCLC (11%) and not detected in 38 patients with squamous cell carcinomas. The incidences of RBM10 mutation were higher in tumors with EGFR mutation (21%) and tumors with KRAS mutation (12%) compared with those without EGFR/KRAS mutations (2%, P < .001 and P = .07, respectively). In tumors with EGFR mutation (N = 68), RBM10 mutation was significantly associated with age (> 76 years, P < .01), the presence of ground-glass opacity (P < 0.05), and histological grade 1 (P < .05). We observed mutually exclusive relationships between RBM10 mutation, TP53 mutation, and MDM2 gene amplification, and a high incidence of RBM10 mutation or MDM2 gene amplification in tumors with EGFR L858R mutation/uncommon mutation.
Conclusion:
RBM10 mutation is frequent in Japanese patients with NSCLC with EGFR mutation, especially those with L858R or uncommon mutations, and was associated with late-onset and features of indolent tumor growth.
Insights
RNA-binding motif 10 (RBM10) mutations are common in non-small-cell lung cancer (NSCLC) with EGFR mutations, particularly in Japanese patients. These RBM10 mutations are linked to slower tumor growth and later onset.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- RNA-binding motif 10 (RBM10) mutations in non-small-cell lung cancer (NSCLC) correlate with reduced sensitivity to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors.
- The prevalence of RBM10 mutations in early-stage NSCLC and their associations with other genetic alterations remain largely uncharacterized.
Purpose of the Study:
- To investigate the incidence and clinical significance of RBM10 mutations in surgically resected NSCLC.
- To explore the relationship between RBM10 mutations and other common driver mutations, including EGFR and KRAS.
Main Methods:
- Analysis of clinical and whole-exome sequencing genomic data from 190 NSCLC patients undergoing surgical resection.
- Prospective, multicenter observational study design.
- Statistical analysis to determine mutation frequencies and associations.
Main Results:
- RBM10 mutations were identified in 11% of nonsquamous NSCLC cases but not in squamous cell carcinomas.
- Higher incidences of RBM10 mutations were observed in tumors with EGFR (21%) and KRAS (12%) mutations compared to those without.
- In EGFR-mutated tumors, RBM10 mutations were associated with older age, ground-glass opacity, and lower histological grade, suggesting indolent growth patterns.
Conclusions:
- RBM10 mutations are frequent in Japanese NSCLC patients with EGFR mutations, especially L858R or uncommon variants.
- RBM10 mutations are associated with clinical features indicative of indolent tumor behavior and late-onset disease.
More Related Videos
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:23Abnormal Proliferation
02:38The Ras Gene
Ras is a...
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...