ALK (anaplastic lymphoma kinase) is oncogenic in several tumours and has recently been identified as a predisposition gene for familial NB (neuroblastoma) harbouring mutations in the TKD (tyrosine kinase domain). We have analysed a large set of sporadic human NB primary tumours of all clinical stages for chromosomal re-arrangements using a CGH (comparative genomic hybridization) array (n=108) and mutations of the ALK gene (n=90), and expression of ALK and related genes (n=19). ALK amplification or in-gene re-arrangements were found in 5% of NB tumours and mutations were found in 11%, including two novel not previously published mutations in the TKD, c.3733T>A and c.3735C>A. DNA mutations in the TKD and gene amplifications were only found in advanced large primary tumours or metastatic tumours, and correlated with the expression levels of ALK and downstream genes as well as other unfavourable features, and poor outcome. The results of the present study support that the ALK protein contributes to NB oncogenesis providing a highly interesting putative therapeutic target in a subset of unfavourable NB tumours.
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December 2008
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Research Article|
November 12 2008
High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours
Helena Carén;
Helena Carén
*Department of Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden
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Frida Abel;
Frida Abel
*Department of Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden
†Department of Mathematical Statistics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden
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Per Kogner;
Per Kogner
‡Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska Hospital, SE-17176 Stockholm, Sweden
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Tommy Martinsson
Tommy Martinsson
1
*Department of Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden
1To whom correspondence should be addressed (email tommy.martinsson@gu.se).
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Publisher: Portland Press Ltd
Received:
September 11 2008
Revision Received:
October 06 2008
Accepted:
October 07 2008
Accepted Manuscript online:
October 07 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 416 (2): 153–159.
Article history
Received:
September 11 2008
Revision Received:
October 06 2008
Accepted:
October 07 2008
Accepted Manuscript online:
October 07 2008
Citation
Helena Carén, Frida Abel, Per Kogner, Tommy Martinsson; High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochem J 1 December 2008; 416 (2): 153–159. doi: https://doi.org/10.1042/BJ20081834
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