Somatic and germline mutations of the anaplastic lymphoma kinase (ALK) gene were recently described in neuroblastoma (NB). In this study, we investigated the association of ALK copy number alterations with copy number status 2p24.1 amplicon harboring DEAD box polypeptide 1 (DDX1), MYCN and neuroblastoma-amplified (NAG) genes in 90 primary tumors of sporadic NB cases by multiplex ligation-dependent probe amplification (MLPA). We also performed mutation analysis of ALK gene by directly sequencing the exons 20-28 which cover the region that encodes juxtamembrane and kinase domains. A total of 39 (43.3%) NB cases revealed copy numbers alterations of ALK gene. There was highly significant association of ALK copy number gains with gains of one or more of the genes at 2p24.1 (DDX1, MYCN or NAG) in MYCN unamplified tumors (P<0.000). In addition, 15 of 17 MYCN amplified cases (88.2%) had aberrant ALK status. Solitary gain of ALK with normal copy number status of all other genes was observed only in one case. DNA sequencing of exons 20-28 of ALK revealed two different nucleotide changes in three cases leading to amino acid substitutions of F1245V and R1275Q in tyrosine kinase domain. In conclusion, the frequency of ALK mutations in NB is low and solitary copy number change of it is rarely observed.
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