Analysis of these previously uncharacterised ALK mutants and comparison with ALK(F1174) mutants suggests that ALK mutations observed in neuroblastoma fall into three classes.
Here, we show that both wild-type and gain-of-function mutants in ALK are able to stimulate transcription at the MYCN promoter and initiate mRNA transcription of the MYCN gene in both neuronal and neuroblastoma cell lines.
Chromosomal translocations and single point mutations involving the Anaplastic Lymphoma Kinase (ALK) gene have been described in several human tumors, including anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NCSLC), inflammatory myofibroblastic tumor (IMT) and neuroblastoma.
Our findings demonstrate a pathogenic role for ALK(F1174L) in neuroblastomas overexpressing MYCN and suggest a strategy for improving targeted therapy for ALK-positive neuroblastoma.
In neuroblastoma, activating point mutations in the ALK kinase domain can drive disease progression, with the two most common mutations being F1174L and R1275Q.
Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALK-rearrangement in lung cancer: a comprehensive study of Caucasian non-smokers.
We report the case of a non-smoking 40-year-old woman, diagnosed with metastatic poorly differentiated papillary adenocarcinoma of the lung harbouring the ALK fusion gene.
We report the case of an adenocarcinoma of the lung associated with metachronous miliary brain and lung metastases with an echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation.
Chromosomal rearrangements leading to constitutive activation of anaplastic lymphoma receptor tyrosine kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy with the ALK inhibitor crizotinib.
Chromosomal translocations and single point mutations involving the Anaplastic Lymphoma Kinase (ALK) gene have been described in several human tumors, including anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NCSLC), inflammatory myofibroblastic tumor (IMT) and neuroblastoma.
2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazines: new variant of an old template and application to the discovery of anaplastic lymphoma kinase (ALK) inhibitors with in vivo antitumor activity.
We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.
Here we report the identification of a secondary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory myofibroblastic tumor (IMT) harboring a RANBP2-ALK translocation who progressed while on crizotinib therapy.