ArticleBMC medicine2023
Rare mutation-dominant compound EGFR-positive NSCLC is associated with enriched kinase domain-resided variants of uncertain significance and poor clinical outcomes.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Landscape of Chinese Lung Cancer Patients With Compound Mutations and Acquired Resistance Alterations: A Retrospective Study.International journal of cancer · 2026Article
- Comparative analysis of genomic profiles and clinical outcomes in cholangiocarcinoma and gallbladder cancer.Scientific reports · 2026Article
- Individualized management strategies for advanced non-small cell lung cancer withOncology letters · 2026Article
- EGFR p.V774M/p. the S768I Compound Mutation in NSCLC Is a Good Prognostic Marker for IPHC- and Furmonertinib-Based Treatment: A Case Report.Cancer reports (Hoboken, N.J.) · 2026Article
- Deciphering the Structural Basis of Allosteric Inhibition of Mutant Epidermal Growth Factor Receptor and Identification of Novel Inhibitors.Computational and structural biotechnology journal · 2026Article
- Evaluation of gefitinib alone or combined with bevacizumab in patients withTranslational lung cancer research · 2025Article
- Single-cell RNA profiling reveals an immunosuppressive microenvironment inTranslational lung cancer research · 2025Article
- EGFR exon 20 insertions mutation in lung adenocarcinoma and its response by high-dose of Furmonertinib: a real-world study.BMC cancer · 2025Article
- Molecular characteristics and responses to EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients with EGFR exon 19 insertions.BMC medicine · 2025Article
- Addition of bevacizumab to gefitinib plus chemotherapy as first-line therapy in EGFR L858R mutate advanced non-small cell lung cancer patients.Frontiers in pharmacology · 2025Article
- The prospect of substrate-based kinase inhibitors to improve target selectivity and overcome drug resistance.Chemical science · 2024Review
- Comprehensive genomic profiling of pulmonary spindle cell carcinoma using tissue and plasma samples: insights from a real-world cohort analysis.The journal of pathology. Clinical research · 2024Article
- An epidermal growth factor receptor compound mutation of L858R with S768I in advanced non-small-cell lung cancer: a case report.Journal of medical case reports · 2024Article
- Simulation analysis of EGFR mutation detection: Oncomine Dx target test and AmoyDx panel impact on lung cancer treatment decisions.Scientific reports · 2024Article
- Article
- The differential prognostic implications of PD-L1 expression in the outcomes of Filipinos withTranslational lung cancer research · 2023Article
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10 authors.
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Abstract
backgroundCompound epidermal growth factor receptor (EGFR) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated.
methodsWe retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). Prognosis and drug resistance to first-line TKIs were analyzed in 174 and 95 patients, respectively.
resultsCompound EGFR mutations were enriched with EGFR exon 21 p.L858R and rare mutations, but not 19-Del (P < 0.001). The common + rare and rare + rare subtypes had fewer concurrent mutations in the PI3K pathway (P = 0.032), while the rare + rare and common + VUSs subtypes showed increased association with smoking- and temozolomide-related mutational signatures, respectively (P < 0.001). The rare mutation-dominant subtypes (rare + VUSs and rare + rare) had the worst clinical outcomes to first-line TKIs (P < 0.001), which was further confirmed using an external cohort (P = 0.0066). VUSs in the rare + VUSs subtype selectively reside in the EGFR kinase domain (P < 0.001), implying these tumors might select additional mutations to disrupt the regulation/function of the kinase domain.
conclusionsDifferent subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments.
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