Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma
Tumour and blood DNA from a 21-month-old Caucasian American male with stage 4 neuroblastoma were sequenced as part of the TARGET project. The tumour was characterised by MYCN amplification using fluorescence in situ hybridisation (FISH), unfavourable histology () and a DNA index of 1.908. Whole genome, exome, and transcriptome sequencing were performed using the Illumina Genome Analyzer. Data were processed as previously described (; ). Sequencing revealed a heterozygous R1646STOP variant in both tumour and blood DNA. In the blood genome, eight reads (47%) supported the reference allele G, and nine reads (53%) supported the alternative allele A. In the tumour genome, five sequencing reads (31%) supported the G allele, and eleven reads supported the A allele. Both reference and alternative alleles were expressed in the tumour transcriptome, with nine and seven reads (56% and 44%) supporting the reference and mutant alleles, respectively. The variant was independently verified by Sanger sequencing.