ArticleThe Journal of pathology2018
Genetic instability and recurrent MYC amplification in ALK-translocated NSCLC: a central role of TP53 mutations.
Article in The Journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis.BMC cancer · 2020Pooled it
- Clinicogenomic Characteristics and Treatment Outcomes of Patients With AdvancedJCO precision oncology · 2026Article
- Intratumoral heterogeneity and drug resistance in cancer.Cancer cell international · 2025Review
- Severe skin toxicity and early progression following neoadjuvant ensartinib and surgery in anaplastic lymphoma kinase-positive locally advanced lung cancer: a case report.Frontiers in pharmacology · 2025Article
- Concomitant ALK Fusion and TP53/EGFR Mutation Lead to Adverse Prognostic Outcome.The clinical respiratory journal · 2024Review
- Clinical difference on the variants and co-mutation in a Chinese cohort with ALK-positive advanced non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Assessment of MYC and TERT copy number variations in lung cancer using digital PCR.BMC research notes · 2023Article
- TP53 or CDKN2A/B covariation in ALK/RET/ROS1-rearranged NSCLC is associated with a high TMB, tumor immunosuppressive microenvironment and poor prognosis.Journal of cancer research and clinical oncology · 2023Article
- Editorial: Concomitant pathogenic mutations in oncogene-driven subgroups: when next generation biology meets targeted therapy in NSCLC.Frontiers in oncology · 2023Article
- Article
- Ultra-sensitive molecular detection of gene fusions from RNA using ASPYRE.BMC medical genomics · 2022Article
- Longitudinal monitoring by next-generation sequencing of plasma cell-free DNA in ALK rearranged NSCLC patients treated with ALK tyrosine kinase inhibitors.Cancer medicine · 2022Article
- Alternative Treatment Options to ALK Inhibitor Monotherapy for EML4-ALK-Driven Lung Cancer.Cancers · 2022Review
- Article
- Challenges in the Use of Targeted Therapies in Non-Small Cell Lung Cancer.Cancer research and treatment · 2022Review
- An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.Bosnian journal of basic medical sciences · 2022Review
- Shifting Gears in Precision Oncology-Challenges and Opportunities of Integrative Data Analysis.Biomolecules · 2021Review
- NGS-based liquid biopsy profiling identifies mechanisms of resistance to ALK inhibitors: a step toward personalized NSCLC treatment.Molecular oncology · 2021Article
- Intratumoral Cellular Heterogeneity: Implications for Drug Resistance in Patients with Non-Small Cell Lung Cancer.Cancers · 2021Review
- Germline ALK variations are associated with a poor prognosis in glioma and IDH-wildtype glioblastoma.Journal of neuro-oncology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anaplastic lymphoma kinase (ALK) rearrangement defines a distinct molecular subtype of non-small cell lung cancer (NSCLC). Despite the excellent initial efficacy of ALK inhibitors in patients with ALK+ lung cancer, resistance occurs almost inevitably. To date, there is no reliable biomarker allowing the identification of patients at higher risk of relapse. Here, we analysed a subset of 53 ALK+ tumours with and without TP53 mutation and ALK+ NSCLC cell lines by NanoString nCounter technology. We found that the co-occurrence of early TP53 mutations in ALK+ NSCLC can lead to chromosomal instability: 24% of TP53-mutated patients showed amplifications of known cancer genes such as MYC (14%), CCND1 (10%), TERT (5%), BIRC2 (5%), ORAOV1 (5%), and YAP1 (5%). MYC-overexpressing ALK+ TP53-mutated cells had a proliferative advantage compared to wild-type cells. ChIP-Seq data revealed MYC-binding sites within the promoter region of EML4, and MYC overexpression in ALK+ TP53-mutated cells resulted in an upregulation of EML4-ALK, indicating a potential MYC-dependent resistance mechanism in patients with increased MYC copy number. Our study reveals that ALK+ NSCLC represents a more heterogeneous subgroup of tumours than initially thought, and that TP53 mutations in that particular cancer type define a subset of tumours that harbour chromosomal instability, leading to the co-occurrence of pathogenic aberrations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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