ArticleCancer science2017
Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 12 citations in OpenAlex.
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review.BMC cancer · 2019Pooled it
- High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Advances in the Basic Sciences in Thoracic Oncology in the Last 20 Years and Their Translational Impact.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- Lung cancer in patients who have never smoked - an emerging disease.Nature reviews. Clinical oncology · 2024Review
- Clinical and genomic features of non-small cell lung cancer occurring in families.Thoracic cancer · 2023Article
- State of the structure address on MET receptor activation by HGF.Biochemical Society transactions · 2021Review
- Rapid Disease Progression in a Patient with Advanced NSCLC Harboring a GermlineOncoTargets and therapy · 2021Article
- Impaired ligand-dependent MET activation caused by an extracellular SEMA domain missense mutation in lung cancer.Cancer science · 2019Article
- Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer.Cancer science · 2017Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer accompanied by somatic activating mutations in the epidermal growth factor receptor (EGFR) gene, which is associated with a significant clinical response to the targeted therapy, is frequently found in never-smoking Asian women with adenocarcinoma. Although this implies genetic factors underlying the carcinogenesis, the etiology remains unclear. To gain insight into the pathogenic mechanisms, we sequenced the exomes in the peripheral-blood DNA from six siblings, four affected and two unaffected siblings, of a family with familial EGFR-mutant lung adenocarcinoma. We identified a heterozygous missense mutation in MET proto-oncogene, p.Asn375Lys, in all four affected siblings. Combined with somatic loss of heterozygosity for MET, the higher allele frequency in a Japanese sequencing database supports a causative role of the MET mutation in EGFR-mutant lung cancer. Functional assays showed that the mutation reduces the binding affinity of MET for its ligand, hepatocyte growth factor, and damages the subsequent cellular processes, including proliferation, clonogenicity, motility and tumorigenicity. The MET mutation was further observed to abrogate the ERBB3-mediated AKT signal transduction, which is shared downstream by EGFR. These findings provide an etiological view that the MET mutation is involved in the pathogenesis of EGFR-mutant lung cancer because it generates oncogenic stress that induces compensatory EGFR activation. The identification of MET in a family with familial EGFR-mutant lung cancer is insightful to explore the pathogenic mechanism of not only familial, but also sporadic EGFR-mutant lung cancer by underscoring MET-related signaling molecules.
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