2023 World Conference on Lung Cancer (Posters)-P1.12. Characterization of MET Exon 14 Skipping Analog (Y1003) in Non-Small Cell Lung Cancer (NSCLC)

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This study focuses on the characterization of a rare mutation known as MET Y1003 in non-small cell lung cancer (NSCLC). The mutation leads to increased activation of the MET receptor, an oncogenic tyrosine kinase receptor, due to impaired binding of a protein called c-Cbl. The researchers aimed to molecularly characterize Y1003 and compare it to the more common MET exon 14 skipping mutation (METex14) and MET wildtype (WT) NSCLC.<br /><br />Genomic profiling was conducted on 40,179 NSCLC tumor samples, and Y1003 was identified in 28 patients (0.07%) while METex14 was found in 711 patients (1.77%). The Y1003 cohort had a median age of 78.5 years and predominantly had adenocarcinoma histology. Notable co-alterations with Y1003 included STK11, NF2, and FBXW7. Both Y1003 and METex14 showed increased expression of MET mRNA and co-amplifications of MDM2 and CDK4. Y1003 also exhibited a higher prevalence of PD-L1 Tumor Proportion Score (TPS) 1% but a lower percentage of high tumor mutational burden (TMB) compared to the WT.<br /><br />The study found that both Y1003 and METex14 were associated with immune and inflammatory response pathways, as well as immune checkpoints such as PD-L2 and IDO1, and M2-macrophage infiltration. Additionally, Y1003 was associated with MDM2 and CDK4 co-amplifications, as well as increased expression of IDO1.<br /><br />The researchers concluded that Y1003 has similarities to METex14 in terms of MDM2 and CDK4 co-amplifications and IDO1 expression. Y1003 is also associated with a highly immunogenic tumor microenvironment. Further research is needed to explore targeted treatments for patients with Y1003 mutation.<br /><br />In summary, this study provides a molecular characterization of the rare MET Y1003 mutation in NSCLC and compares it to the more common METex14 mutation. The findings highlight similarities and differences in the molecular and immune landscapes of these mutations, which could have implications for targeted therapies in NSCLC.

Asset Subtitle

So Yeon Kim

Meta Tag

Speaker So Yeon Kim

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

MET Y1003

non-small cell lung cancer

oncogenic tyrosine kinase receptor

c-Cbl

MET exon 14 skipping mutation

genomic profiling

adenocarcinoma histology

MDM2

CDK4

immunogenic tumor microenvironment