ALK, ALK receptor tyrosine kinase, 238

N. diseases: 519; N. variants: 41
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Crizotinib + topo/cyclo showed synergistic cytotoxicity and higher caspase-dependent apoptosis than crizotinib or topo/cyclo alone in neuroblastoma cell lines with ALK aberrations (mutation or amplification). 26438783 2016
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE These lines represent MYCN-amplified, NRAS and ALK mutant neuroblastoma subtypes respectively. 26517508 2015
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Mice with neuroblastomas harbouring the anaplastic lymphoma kinase mutation exhibited a significantly slower R<sub>2</sub>* (P<0.001), consistent with impaired tumour perfusion. 28787429 2017
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. 25071110 2014
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE More recently, genomic DNA amplification and protein overexpression, as well as activating point mutations, of ALK have been described in neuroblastomas. 19275511 2009
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Antitumor activity of the ALK inhibitor TAE684 was evaluated in wild-type or mutated ALK neuroblastoma cell lines and xenografts. 26687816 2016
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Our biochemical and in vivo data provide the preclinical rationale for fast-tracking the development of this agent in children with relapsed/refractory ALK-mutant neuroblastoma. 26554404 2016
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Herein, we have illustrated the dynamic conformational property of wild-type ALK as well as the kinase activation equilibrium variation induced by two neuroblastoma mutations (R1275Q and Y1278S) and ATP binding by performing enhanced sampling accelerated Molecular Dynamics (aMD) simulations. 29638111 2018
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE To address the possibility that ALK activation may occur through genomic rearrangements as detected in other cancers, we first took advantage of high-resolution array-comparative genomic hybridization to search for ALK rearrangements in NB samples. 23139213 2013
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684. 21838707 2011
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE ALK somatic mutation or gene amplification predisposing neuroblastoma development occurs in up to 15 % of neuroblastomas. 22588779 2012
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Moreover, nearly two dozen ALK activating mutations are involved in the pathogenesis of childhood neuroblastomas. 28077299 2017
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Here we show that the anaplastic lymphoma kinase (ALK), originally identified as a fusion kinase in a subtype of non-Hodgkin's lymphoma (NPM-ALK) and more recently in adenocarcinoma of lung (EML4-ALK), is also a frequent target of genetic alteration in advanced neuroblastoma. 18923524 2008
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Further, activating point mutations in the ALK domain have been recently reported in neuroblastoma. 20190816 2010
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Analysis of these previously uncharacterised ALK mutants and comparison with ALK(F1174) mutants suggests that ALK mutations observed in neuroblastoma fall into three classes. 23104988 2013
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Potential molecular targets in neuroblastoma include ALK mutations, p16 deletion and CDK2A mutations; however, targeted therapeutics have not been developed for these factors. 24714808 2014
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE ALK mutations were present in 6.9% of 709 investigated tumors, and mutations were found in similar frequencies in favorable [International Neuroblastoma Staging System (INSS) 1, 2, and 4S; 5.7%] and unfavorable (INSS 3 and 4; 7.5%) neuroblastomas (P = 0.087). 20719933 2010
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Although expression of ALK F1174L resulted in enhanced proliferation of sympathetic ganglion progenitors and increased the size of the sympathetic ganglia, it was insufficient to cause neuroblastoma. 31218818 2019
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE This pair of cell lines represents a valuable pre-clinical model of clonal evolution of ALK mutations associated with neuroblastoma progression. 27888620 2016
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE One of the major causes of sporadic NB is known to be MYCN amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible for familial NB. 29371588 2018
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e.g., MYCN amplification status, ALK mutation status, chromosome arm 1p, 11q and/or 17q status, sensitivity to pharmacologic perturbation). 28350380 2017
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE ALK mutations were present in 10.4% of neuroblastoma samples. 22142829 2012
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. 18990089 2008
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE Here, we report similar basal patterns of ALK phosphorylation between the neuroblastoma IMR-32 cell line, which expresses only the wild-type receptor (ALK(WT)), and the SH-SY5Y cell line, which exhibits a heterozygous ALK F1174L mutation and expresses both ALK(WT) and ALK(F1174L) receptors. 22479414 2012
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.700 GeneticVariation disease BEFREE The case of the anaplastic lymphoma kinase (ALK) nicely exemplifies this, and cell line profiling has revealed that ALK mutations present in a subset of anaplastic large cell lymphomas (ALCLs), non-small cell lung cancers (NSCLCs), and neuroblastomas appear to sensitize cancer cells to treatment with selective ALK kinase inhibitors. 19393834 2009