rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
To study the contribution of ALK mutations in NB initiation and progression, we reprogrammed fibroblasts from two related NB patients carrying germline mutations in ALK (R1275Q) using non-integrating Sendai virus.
|
30605844 |
2019 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Combined treatment with alectinib and vorinostat might be a novel therapeutic option for NB harboring the ALK R1275Q mutation.
|
31262882 |
2019 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
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 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6 µM PCI-34051 or 10 µM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count.
|
29515255 |
2018 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Using both Sanger and targeted deep sequencing, this study describes the identification of distinct ALK mutations in these paired cell lines, including the rare R1275L mutation, which has not previously been reported in a neuroblastoma cell line.
|
27888620 |
2016 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
A 77-gene ALK signature was established and successfully validated in primary neuroblastoma samples, in a neuroblastoma cell line with ALK(F1174L) and ALK(R1275Q) regulable overexpression constructs and in other ALKomas.
|
25805801 |
2015 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse models, and cooperate with MYCN in the oncogenic process.
|
24947326 |
2014 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The R1275Q neuroblastoma mutant and certain ATP-competitive inhibitors stabilize alternative activation loop conformations of anaplastic lymphoma kinase.
|
22932897 |
2012 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The most frequent ALK mutations in neuroblastoma cause amino acid substitutions (F1174L and R1275Q) in the intracellular tyrosine kinase domain of the intact ALK receptor.
|
22072639 |
2011 |
rs113994087
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
We detected the ALK mutation (F1174C and R1275Q) in 2 (3.7%) of the 54 NB specimens.
|
21940108 |
2011 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Altogether, we report for the first time that the expression of the human ALK-F1174L mutation in NCCs during embryonic development profoundly disturbs early sympathetic progenitor differentiation, in addition to increasing their proliferation, both mechanisms being potential crucial events in NB oncogenesis.
|
31058082 |
2019 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
However, lethal neuroblastoma</span> frequently developed in mice co-expressing ALK F1174L and MYCN, even in a genetic background where MYCN alone does not cause overt tumors.
|
31218818 |
2019 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6 µM PCI-34051 or 10 µM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count.
|
29515255 |
2018 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT.
|
26616860 |
2016 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
A 77-gene ALK signature was established and successfully validated in primary neuroblastoma samples, in a neuroblastoma cell line with ALK(F1174L) and ALK(R1275Q) regulable overexpression constructs and in other ALKomas.
|
25805801 |
2015 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse models, and cooperate with MYCN in the oncogenic process.
|
24947326 |
2014 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Intrinsic susceptibility-MRI could thus potentially provide a non-invasive and clinically-exploitable method to help identifying children with MYCN-driven neuroblastoma harboring the ALK(F1174L) mutation at the time of diagnosis.
|
24667968 |
2014 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
We have shown that the combination of crizotinib and an inhibitor of downstream signaling induces a favorable response in transgenic mice bearing ALK(F1174L)/MYCN-positive neuroblastoma.
|
25228590 |
2014 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here we present the evidence that murine neural crest progenitor cells can give rise to neuroblastoma upon transformation with MYCN or ALK(F1174L).
|
22484425 |
2013 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
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 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Targeted ALK(F1174L) and MYCN coexpression revealed a strong synergism in inducing neuroblastoma with minimal chromosomal aberrations, suggesting that fewer secondary hits are required for tumor induction if both oncoproteins are targeted.
|
22764207 |
2012 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The most frequent ALK mutations in neuroblastoma cause amino acid substitutions (F1174L and R1275Q) in the intracellular tyrosine kinase domain of the intact ALK receptor.
|
22072639 |
2011 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, which play a major role in neuroblastoma, were recently identified.
|
20632993 |
2010 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers.
|
21030459 |
2010 |
rs281864719
|
|
Central neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Furthermore, two human neuroblastoma cell lines harbouring the F1174L</span> mutation were also sensitive to the inhibitor.
|
18923525 |
2008 |