Activating mutations in ALK provide a therapeutic target in neuroblastoma

@article{George2008ActivatingMI,
  title={Activating mutations in ALK provide a therapeutic target in neuroblastoma},
  author={Rani E. George and Takaomi Sanda and Megan Hanna and Stefan Fr{\"o}hling and William Luther and Jianming Zhang and Yebin Ahn and Wenjun Zhou and Wendy B. London and Patrick W. McGrady and Liquan Xue and Sergey Zozulya and Vladim{\'i}r Gregor and Thomas R. Webb and Nathanael S. Gray and Dwight Gary Gilliland and Lisa R Diller and Heidi Greulich and Stephan W. Morris and Matthew L Meyerson and A. Thomas Look},
  journal={Nature},
  year={2008},
  volume={455},
  pages={975 - 978}
}
Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer. High-risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal. Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non-synonymous sequence variations were… 
Advanced Neuroblastoma: Role of ALK Mutations
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TLDR
This pair of cell lines represents a valuable pre-clinical model of clonal evolution of ALK mutations associated with neuroblastoma progression and reveals differences between the paired cell lines, and overall NBLW-R cells with the F1174L mutation were more resistant to ALK inhibitor induced apoptosis compared with N BLW cells.
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TLDR
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TLDR
A mechanistic interaction in which ALK upregulates MYCN transcription is described, and clinical trials emerging to develop transcriptional inhibitors of MYCN, and to identify effective inhibitors of ALK in neuroblastoma patients are discussed.
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TLDR
This review will give a comprehensive overview on ALK inhibitors in clinical use in high-risk NBL and on the potential and limitations of novel inhibitors.
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TLDR
A mechanistic interaction in which ALK upregulates MYCN transcription is described, and clinical trials emerging to develop transcriptional inhibitors of MYCN, and to identify effective inhibitors of ALK in neuroblastoma patients are discussed.
Anaplastic Lymphoma Kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells
TLDR
It is indicated that ALK signalling regulates initiation of transcription of the MYCN gene providing a possible explanation for the poor clinical outcome observed when MYCN is amplified together with activated ALK.
Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer
Neuroblastoma is a common extracranial solid tumour of childhood, responsible for 15% of cancer-related deaths in children. Prognoses vary from spontaneous remission to aggressive disease with
Characterization of rearrangements involving the ALK gene reveals a novel truncated form associated with tumor aggressiveness in neuroblastoma.
TLDR
Results indicate that genomic rearrangements constitute an alternative mechanism to ALK point mutations resulting in receptor activation, and may be implicated in tumor aggressiveness.
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