Summary Genetic studies have established anaplastic lymphoma kinase (ALK), a cell surface receptor tyrosine kinase, as a tractable molecular target in neuroblastoma. We describe comprehensive genomic, biochemical, and computational analyses of ALK mutations across 1596 diagnostic neuroblastoma samples. ALK tyrosine kinase domain mutations occurred in 8% of samples; at three hotspots plus 13 minor sites – and correlated significantly with poorer survival in high- and intermediate-risk neuroblastoma. Biochemical and computational studies distinguished oncogenic (constitutively activating) from non-oncogenic mutations and allowed robust computational prediction of their effects. We also established differential in vitro crizotinib sensitivity of mutated variants. Our studies identify ALK genomic status as a clinically important therapeutic stratification tool in neuroblastoma, and will allow tailoring of ALK-targeted therapy to specific mutations.

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Contemporary medical imaging is a cornerstone of care for children with cancer. As 5-year survival rates for children with cancer exceed 80%, imaging technologies have evolved in parallel to include a wide array of modalities. Here, we overview the risks and benefits associated with commonly used imaging modalities and survey the current landscape of medical imaging for children with cancer. We find evidence-based imaging guidelines to assist in protocol development and to guide decision-making for optimal patient care are often lacking. The substantial variation in protocol-based recommendations for imaging both during and following therapy may hinder optimal clinical research and clinical care for children with cancer.