ArticleNature2008
Identification of ALK as a major familial neuroblastoma predisposition gene.
Article in Nature, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02780128 (Next Generation Personalized Neuroblastoma Therapy), which is not on this map. Cited by 650 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Next Generation Personalized Neuroblastoma Therapy (The NEPENTHE Trial)
Who cites it
650 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,397 citations in OpenAlex.
- Research status and development trends of omics in neuroblastoma a bibliometric and visualization analysis.Frontiers in oncology · 2024Pooled it
- Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology.Cancer metastasis reviews · 2022Pooled it
- Extracellular Vesicles: A New Source of Biomarkers in Pediatric Solid Tumors? A Systematic Review.Frontiers in oncology · 2022Pooled it
- 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
- NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.Cancer discovery · 2024Trial
- Integrated miRNA-Target Gene Analysis Reveals Complementary Molecular Biomarkers and Regulatory Networks in Pediatric Neuroblastoma.International journal of molecular sciences · 2026Article
- Unveiling the Prevalence and Surgical Burden of Neurocristopathies: A Scoping Review and Statistical Analysis.Research square · 2026Article
- The Role of Precision Medicine in Neuroblastoma: Targeted Therapies and Personalized Approaches-A Narrative Review.Health science reports · 2026Article
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- A Bayesian-Based Integrative Bioinformatics Analysis Nominates Oncogenic Drivers in Neuroblastoma.Clinical and translational science · 2026Article
- Olive Leaf Extract Health-Promoting and Anti-Tumor Properties: An Adjunct Therapy in Pediatric Oncology?Nutrients · 2026Review
- Article
- Integrating next-generation sequencing into the routine neuroblastoma workflow identifies actionable genomic alterations and reduces low-yield karyotype testing.Virchows Archiv : an international journal of pathology · 2026Article
- Established and Emerging Therapies for High-Risk Neuroblastoma.Paediatric drugs · 2026Review
- Pathology of peripheral neuroblastic tumors.Diagnostic pathology · 2026Review
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- Diagnosis and management of neuroblastoma in children.World journal of pediatric surgery · 2026Review
- Targeted immunotherapies for anaplastic lymphoma kinase-positive pediatric tumors: current advances and future perspectives.Frontiers in immunology · 2026Review
- Integrative precision oncology in neuroblastoma: multi-omics biomarkers, molecular targets, and immunotherapeutic strategies.Frontiers in oncology · 2026Review
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
590 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.