Whole-Exome Sequencing Reveals Novel Candidate Driver Mutations and Potential Druggable Mutations in Patients with High-Risk Neuroblastoma

Neuroblastoma is the most prevalent solid tumor in early childhood, with a 5-year overall survival rate of 40-60% in high-risk cases. Therefore, the identification of novel biomarkers for the diagnosis, prognosis, and therapy of neuroblastoma is crucial for improving the clinical outcomes of these patients. In this study, we conducted the whole-exome sequencing of 48 freshly frozen tumor samples obtained from the Biobank. Somatic variants were identified and selected using a bioinformatics analysis pipeline. The mutational signatures were determined using the Mutalisk online tool. Cancer driver genes and druggable mutations were predicted using the Cancer Genome Interpreter. The most common mutational signature was single base substitution 5. <i>MUC4</i>, <i>MUC16</i>, and <i>FLG</i> were identified as the most frequently mutated genes. Using the Cancer Genome Interpreter, we identified five recurrent cancer driver mutations spanning <i>MUC16</i>, <i>MUC4</i>, <i>ALK</i>, and <i>CTNND1</i>, with the latter being novel and containing a missense mutation, R439C. We also identified 11 putative actionable mutations including <i>NF1</i> Q1798*, Q2616*, and S636X, <i>ALK</i> F1174L and R1275Q, <i>SETD2</i> P10L and Q1829E, <i>BRCA1</i> R612S, <i>NOTCH1</i> D1670V, <i>ATR</i> S1372L, and <i>FGFR1</i> N577K. Our findings provide a comprehensive overview of the novel information relevant to the underlying molecular pathogenesis and therapeutic targets of neuroblastoma.