ArticleTranslational oncology2011
The neuroblastoma ALK(I1250T) mutation is a kinase-dead RTK in vitro and in vivo.
Article in Translational oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Novel activating SNRNP70-ALK fusion in congenital infant-type hemispheric glioma displays clinical response to lorlatinib: a case-report.NPJ precision oncology · 2026Article
- Review
- Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer.International journal of molecular sciences · 2021Review
- Article
- Targeting anaplastic lymphoma kinase in neuroblastoma.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2019Review
- 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
- Anaplastic lymphoma kinase L1198F and G1201E mutations identified in anaplastic thyroid cancer patients are not ligand-independent.Oncotarget · 2017Article
- A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer.Oncogene · 2016Article
- Article
- ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma.Cancer cell · 2014Article
- Wild-type ALK and activating ALK-R1275Q and ALK-F1174L mutations upregulate Myc and initiate tumor formation in murine neural crest progenitor cells.Oncotarget · 2014Article
- Article
- ALK-rearrangements and testing methods in non-small cell lung cancer: a review.Genes & cancer · 2014Review
- Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology.Nature reviews. Cancer · 2013Review
- Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.Disease models & mechanisms · 2013Article
- Effective Alu repeat based RT-Qpcr normalization in cancer cell perturbation experiments.PloS one · 2013Article
- Targeting ALK in neuroblastoma--preclinical and clinical advancements.Nature reviews. Clinical oncology · 2012Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Activating mutations in the kinase domain of anaplastic lymphoma kinase (ALK) have recently been shown to be an important determinant in the genetics of the childhood tumor neuroblastoma. Here we discuss an in-depth analysis of one of the reported gain-of-function ALK mutations-ALK(I1250T)-identified in the germ line DNA of one patient. Our analyses were performed in cell culture-based systems and subsequently confirmed in a Drosophila model. The results presented here indicate that the germ line ALK(I1250T) mutation is most probably not a determinant for tumor initiation or progression and, in contrast, seems to generate a kinase-dead mutation in the ALK receptor tyrosine kinase (RTK). Consistent with this, stimulation with agonist ALK antibodies fails to lead to stimulation of ALK(I1250T) and we were unable to detect tyrosine phosphorylation under any circumstances. In agreement, ALK(I1250T) is unable to activate downstream signaling pathways or to mediate neurite outgrowth, in contrast to the activated wild-type ALK receptor or the activating ALK(F1174S) mutant. Identical results were obtained when the ALK(I1250T) mutant was expressed in a Drosophila model, confirming the lack of activity of this mutant ALK RTK. We suggest that the ALK(I1250T) mutation leads to a kinase-dead ALK RTK, in stark contrast to assumed gain-of-function status, with significant implications for patients reported to carry this particular ALK mutation.
Identifiers
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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.