High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours.
Biochem J. 2008 Oct 7;
Authors: Carén H, Abel F, Kogner P, Martinsson T
Anaplastic lymphoma kinase (ALK) is oncogenic in several tumours and recently identified as a predisposition gene for familial neuroblastoma (NB) harbouring mutations in the tyrosine kinase domain (TKD). We have analysed a large set of sporadic human NB primary tumours of all clinical stages for chromosomal re-arrangements using array-CGH (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 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 primaries or metastatic tumours and correlated with the expression levels of ALK and downstream genes as well as other unfavourable features and poor outcome. Our data support that the ALK protein contribute to NB oncogenesis providing a highly interesting putative therapeutic target in a subset of unfavourable NB tumours.
PMID: 18840093 [PubMed - as supplied by publisher]