Patient: 49-year-old male, non-smoker, diagnosed with Stage IV lung adenocarcinoma with multiple bilateral pulmonary nodules and liver metastases.
Clinical Testing:
Alterations:
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MET exon 14 skipping (splice-site variant; ctDNA VAF 0.7%; RNA confirmed; not detected in tissue DNA)
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TP53 p.G245D (ctDNA VAF 3.5%; tissue DNA 9%)
Additional Biomarkers:
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High TMB: Plasma 21%, Tissue 16%
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PD-L1 TPS: 65% (tissue)
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CD274 (PD-L1) RNA expression: 8.83
Genes / Pathways Affected:
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MET-driven oncogenic pathway
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MAPK/PI3K signaling alterations
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Genomic instability / TP53 tumor suppressor pathway
Treatment Options:
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MET inhibitors (due to validated MET exon 14 skipping)
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Immunotherapy (given high TMB and high PD-L1 expression)
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Combination targeted + immunotherapy approaches (informed by multi-omic tumor heterogeneity)
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Clinical-trial–based targeted combinations leveraging MAPK/PI3K pathway disruptions and MET-driven biology
Indication:
Advanced metastatic lung adenocarcinoma with heterogeneous tumor biology, requiring integrated tissue–liquid–RNA multi-omic profiling to identify actionable targets.
Research Findings:
Multi-omic tumor–liquid–normal matched profiling identified a true actionable MET exon 14 skipping variant despite low ctDNA levels, validated through RNA testing. High TMB and PD-L1 expression support strong immunotherapy potential. MAPK/PI3K signaling alterations and TP53 mutation reflect aggressive biology and genomic instability. Integrated DNA–RNA–protein analysis provided clinically meaningful insights that single-sample testing would have missed, enabling precision targeting for advanced disease management.