|
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 |
|
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 |
|
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 |
|
Neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT.
|
26616860 |
2016 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Expression of MYCN or ALK(F1174L), one of the oncogenic ALK variants identified in primary neuroblastomas, enabled these cells to grow independently of c-MycER(T) activity in vitro and caused formation of neuroblastoma-like tumors in vivo in contrast to parental JoMa1 cells and JoMa1 cells-expressing TrkA or GFP.
|
22484425 |
2013 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers.
|
21030459 |
2010 |
|
Neuroblastoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Furthermore, two human neuroblastoma cell lines harbouring the F1174L</span> mutation were also sensitive to the inhibitor.
|
18923525 |
2008 |