ArticleScientific reports2019
Low Frequency ALK Hotspots Mutations In Neuroblastoma Tumours Detected By Ultra-deep Sequencing: Implications For ALK Inhibitor Treatment.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 23 citations in OpenAlex.
- Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High-Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- A structure-based virtual screening approach to identify novel anaplastic lymphoma kinase inhibitors.Journal of molecular modeling · 2026Article
- Brain metastases from non-small cell lung cancer: molecular subtypes and emerging CNS-directed precision therapies.Frontiers in oncology · 2026Review
- Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.Molecular neurobiology · 2025Review
- 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.Current oncology reports · 2025Review
- Article
- Comparative Atomistic Insights on Apo and ATP-I1171N/S/T in Nonsmall-Cell Lung Cancer.ACS omega · 2023Article
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
- Genomic ALK alterations in primary and relapsed neuroblastoma.British journal of cancer · 2023Article
- Overview of the 2022 WHO Classification of Paragangliomas and Pheochromocytomas.Endocrine pathology · 2022Review
- Targeting Oncogenic Transcriptional Networks in Neuroblastoma: From N-Myc to Epigenetic Drugs.International journal of molecular sciences · 2021Review
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- Frequency and Prognostic Impact ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Article
- Differential Impact ofJCO precision oncology · 2021Article
- Developing preclinical models of neuroblastoma: driving therapeutic testing.BMC biomedical engineering · 2019Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (>5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7-60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation spectrum in relation to neuroblastoma tumours genomic subtypes could be detected although there was a paucity of ALK mutations among 11q-deleted tumors. As ALK mutations status opens up an excellent opportunity for application of small molecule inhibitors targeting ALK, early and sensitive detection of ALK alterations is clinically important considering its potential role in tumour progression.
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