ArticleNature2008
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.
Article in Nature, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 435 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
435 citing papers in PubMed, 2 syntheses or guidelines pooled it, 890 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
- Precision gene editing in infant neuroblastoma: a review of nanoparticle: enabled CRISPR/Cas9 therapies.Molecular biology reports · 2026Review
- A functional landscape for chromosome 17q in neuroblastoma: balancing replication stress and genomic stability.British journal of cancer · 2026Review
- Integrative precision oncology in neuroblastoma: multi-omics biomarkers, molecular targets, and immunotherapeutic strategies.Frontiers in oncology · 2026Review
- Chromosomal instability degrades developmental phenotypes essential for anti-GD2 immunotherapy outcomes in high-risk neuroblastoma.Cell reports. Medicine · 2025Article
- Kinome Reprogramming of G2/M Kinases and Repression of MYCN Contribute to Superior Efficacy of Lorlatinib in ALK-Driven Neuroblastoma.Molecular cancer therapeutics · 2025Article
- Pulmonary Toxicity Associated With Concurrent Lorlatinib and Anti-GD2 Monoclonal Antibody Therapy in Patients With Neuroblastoma.Pediatric blood & cancer · 2025Article
- A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers.Nature communications · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.Current oncology reports · 2025Review
- Anaplastic Lymphoma Kinase Inhibition Therapy for Hereditary Neuroblastoma.JCO precision oncology · 2025Article
- The relative contributions of genetic and non-genetic factors to the risk of neuroblastoma.Pediatric investigation · 2025Review
- Article
- Therapeutic benefit of the dual ALK/FAK inhibitor ESK440 in ALK-driven neuroblastoma.Neoplasia (New York, N.Y.) · 2025Article
- Neuroblastoma susceptibility and association of N7-methylguanosine modification gene polymorphisms: multi-center case-control study.Pediatric research · 2025Article
- USP44 Overexpression Drives a MYC-Like Gene Expression Program in Neuroblastoma through Epigenetic Reprogramming.Molecular cancer research : MCR · 2024Article
- Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis.Cancer research communications · 2024Article
- Altered methylation of imprinted genes in neuroblastoma: implications for prognostic refinement.Journal of translational medicine · 2024Article
- Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
375 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments.
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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.