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

P1.12. Characterization of MET Exon 14 Skipping Analog (Y1003) in Non-Small Cell Lung Cancer (NSCLC) - PDF(Slides)

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The study aimed to characterize the MET exon 14 skipping analog (Y1003) mutation in non-small cell lung cancer (NSCLC) and compare it to the MET exon 14 (METex14) skipping mutation and MET wildtype (WT). The Y1003 mutation leads to sustained activation of the MET tyrosine kinase receptor. The researchers analyzed 40,179 NSCLC samples using DNA-based next-generation sequencing and whole-transcriptome sequencing. They assessed mutations, gene amplifications, immune-related pathways, immune cell infiltrates, and expression of immune checkpoint genes.<br /><br />The results showed that METex14 skipping tumors and Y1003 analog tumors had co-amplifications with MDM2 and CDK4, which could be potential targets for therapy. PDL1 positivity was increased, and tumor mutation burden (TMB) was reduced in Y1003 analog tumors. These tumors also exhibited enrichment in PD-L2 and IDO1 expression, interferon response pathways, and M2 macrophage infiltration compared to MET WT tumors. The Y1003 analog tumors had a different histological distribution compared to MET WT tumors and were more frequently observed in females.<br /><br />The study also found that tumors harboring the METex14 skipping analog mutation were enriched for mutations in FBXW7, NF2, and STK11 compared to METex14 skipping tumors. In addition, the expression of MDM2, CDK4, and HMGA2 was increased in METex14 skipping and Y1003 analog tumors compared to MET WT tumors.<br /><br />Overall, the findings suggest that the Y1003 analog mutation in METex14 skipping tumors has similar molecular and immune characteristics to METex14 skipping tumors. These results provide insights into the underlying mechanisms and potential therapeutic targets associated with the Y1003 analog mutation in NSCLC.

Asset Subtitle

So Yeon Kim

Meta Tag

Speaker So Yeon Kim

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

MET exon 14 skipping analog

Y1003 mutation

non-small cell lung cancer

NSCLC

METex14 skipping mutation

MET wildtype

MDM2

CDK4

PDL1 positivity

tumor mutation burden