RBM10 (RNA Binding Motif Protein 10)

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.

NSCLCs harboring ECD-ERBB2 mutations are associated with a unique clinico-genomic phenotype and improved outcomes with first-line chemoimmunotherapy. These findings have implications for optimizing treatment strategies in this disease.

He received afatinib as frontline treatment and showed a partial response; however, the right lung lesion progressed after 14 months of treatment...Because EGFR testing using resected tissue showed only the original mutation, we switched his regimen to pemetrexed and carboplatin...Although an association between MET amplification and rapidly progressive lung cancer has been predicted previously, to the best of our knowledge, this is the first report on the potential contribution of other mutations, such as those in RNA-binding motif 10, during MET-driven rapid progression. Our report highlights the importance of more active utilization of molecular profiling for the emergence of resistance during tyrosine kinase inhibitor use and the early identification of MET amplification and timely initiation of MET-targeted therapy, such as MET inhibitors in combination with EGFR-TKIs, to potentially mitigate rapid disease progression and clinical deterioration.

This study underscores the diverse genetic mutations occurring in NSCLC patients with varying risk factors. The identification of TP53 co-mutations provides critical insights for personalized immunotherapeutic strategies and optimizing treatment outcomes.

Compared to results from established architectures such as Inception-v3 on the same WSIs, our model demonstrated significantly improved performance for most features. With further optimization, our model could support triaging for molecular testing and inform precision treatment strategies for NS-LUAD patients.

Notably, MAP2K1 E102-I103 deletion was frequently observed in pre-invasive samples, which endowed alveolar type II cells with increased growth potential and initiated tumor formation, suggesting that it is a potential driver mutation of LUAD. In summary, our study highlights key molecular changes during the stepwise progression of LUAD, provides insights into the identification of novel therapeutic targets, and helps to define the curative time window for this disease.

This model underscores the pivotal role of TME components in shaping therapeutic outcomes and offers a scalable, clinically translatable tool for personalized risk stratification. Our findings highlight the necessity of integrating microenvironmental insights into MM prognostication and pave the way for microenvironment-informed therapeutic decision-making.

In 10/18 cases, mutational signature analysis revealed a dominant smoking signature, providing evidence of lung origin. Our findings unveil diagnostic pitfalls that may warrant additional evaluation to avoid misdiagnosis of metastatic lung carcinoma as a primary breast carcinoma.

Treatment consisted of Osimertinib and Stereotactic radiosurgery...The molecular features of BM differ from those of the primary tumor. These results indicate that specific brain metastatic clones can also result in systemic progression.

These findings indicate that bladder cancer risk factors, such as sex and smoking, shape the clonal landscape of the normal urothelium. The high number of mutations identified by this approach offers a new strategy to study the functional effect of thousands of mutations in vivo-natural saturation mutagenesis-that can be extended to other human tissues.

Notably, MP60 expression is markedly increased in HCC tissues and is associated with a poorer prognosis. These findings identify MP60 as a potential biomarker and therapeutic target in HCC, linking its oncogenic effects to EMT modulation and tumor progression.