Background: Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood. Recently, several genetic studies have reported oncogenic variations in NB, but the identified mutations were found in a low frequency partly because of the low depth sequencing platforms such as whole exome sequencing. Here, we used high depth targeted sequencing platform (~1000x) covering important 81 oncogenes.
Methods: Genomic DNA from 64 NB patients was sequenced by targeted deep exome sequencing for 81 oncogenes.
Results: Ninety four percent of patients had at least one mutation, and total 256 somatic mutations (186 SNVs and 6 Indels with freq. > 5%) and 107 copy number alterations (53 amplifications and 54 deletions) were identified. However, novel translocation of target genes was not found in this study. The most common mutations were found in the TP53, ROS1, ALK, ATM, EGFR, NF1 and PTCH1 genes. Compared with previous studies, we identified more recurrent variations in TP53 (25.4% in this study vs. 0.4% in previous study), ROS1 (15.9% vs. 1.3%), and ALK (14.3% vs. 9.2%). Interestingly, a deletion (rs3841650) at chromosome 15 was first discovered in IGF1R gene for in our 23 patients. It has been known that the expression of IGF1R gene was related with pathogenesis of NB. From the therapeutic point of view, we identified meaningful mutations such as ALK R1275Q, ALK F1741I, EGFR T790M, HRAS Q61R, and NRAS F12D when considering the use of targeted agents.
Conclusions: Our study using targeted deep sequencing platform provides useful information about genetic landscape of NB.