ArticleDisease models & mechanisms2013
Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.
Article in Disease models & mechanisms, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Review
- Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results.Nature medicine · 2023Article
- ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses viaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- ALK F1174S mutation impairs ALK kinase activity in EML4-ALK variant 1 and sensitizes EML4-ALK variant 3 to crizotinib.Frontiers in oncology · 2023Article
- Multifocal Neuroblastoma and Central Hypoventilation in An Infant with GermlineDiagnostics (Basel, Switzerland) · 2022Article
- Patient-associated mutations in Drosophila Alk perturb neuronal differentiation and promote survival.Disease models & mechanisms · 2022Article
- Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer.International journal of molecular sciences · 2021Review
- HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis.Scientific reports · 2020Article
- Identification of the Wallenda JNKKK as an Alk suppressor reveals increased competitiveness of Alk-expressing cells.Scientific reports · 2020Article
- Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells.Scientific reports · 2019Article
- Targeting anaplastic lymphoma kinase in neuroblastoma.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2019Review
- Low Frequency ALK Hotspots Mutations In Neuroblastoma Tumours Detected By Ultra-deep Sequencing: Implications For ALK Inhibitor Treatment.Scientific reports · 2019Article
- Alectinib, an Anaplastic Lymphoma Kinase Inhibitor, Abolishes ALK Activity and Growth in ALK-Positive Neuroblastoma Cells.Frontiers in oncology · 2019Article
- Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib.Cold Spring Harbor molecular case studies · 2018Article
- The ALK receptor in sympathetic neuron development and neuroblastoma.Cell and tissue research · 2018Review
- Genetic susceptibility to neuroblastoma: current knowledge and future directions.Cell and tissue research · 2018Review
- Review
- Review
- ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the neural crest and derived cells.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Novel Mechanisms of ALK Activation Revealed by Analysis of the Y1278S Neuroblastoma Mutation.Cancers · 2017Article
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15 authors at 8 institutions in 4 countries.
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Abstract
Neuroblastoma is a childhood extracranial solid tumour that is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly requires characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and R1464STOP), which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression, we have employed cell culture-based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position 1174 (F1174I) generates a gain-of-function receptor capable of activating intracellular targets such as ERK (extracellular signal regulated kinase) and STAT3 (signal transducer and activator of transcription 3) in a ligand-independent manner. Analysis of these previously uncharacterised ALK mutants and comparison with ALK(F1174) mutants suggests that ALK mutations observed in neuroblastoma fall into three classes. These classes are: (i) gain-of-function ligand-independent mutations such as ALK(F1174l), (ii) kinase-dead ALK mutants, e.g. ALK(I1250T) (Schönherr et al., 2011a) and (iii) ALK mutations that are ligand-dependent in nature. Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (Xalkori/PF-02341066), albeit with differing levels of sensitivity.
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