High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours.
Journal article, 2008
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.
Mutation
genetics
Gene Amplification
genetics
Neuroblastoma
DNA Primers
Single Nucleotide
mortality
Polymorphism
genetics
pathology
Polymerase Chain Reaction
Humans
Oligonucleotide Array Sequence Analysis
Neoplasm Staging
DNA
Survival Analysis
Protein-Tyrosine Kinases
Receptor Protein-Tyrosine Kinases
Neoplasm
Author
Helena Carén
University of Gothenburg
Frida Abel
University of Gothenburg
Per Kogner
Tommy Martinsson
University of Gothenburg
Biochemical Journal
0264-6021 (ISSN) 1470-8728 (eISSN)
Vol. 416 2 153-9Subject Categories
Clinical Medicine
PubMed
18990089