Figure 4.

ALK mutations detected in neuroblastoma. (Cited and modified from Mosse YP, Laudenslager M, Longo L, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008;455(7215):930-5 ⁽⁸⁾ and Uryu K, Nishimura R, Kataoka K, et al. Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis. Oncotarget. 2017;8(64):107513-29 ⁽²⁶⁾. Copyright of the figure belongs to the authors.)

a. COSMIC frequencies of ALK mutations in neuroblastoma from the published literature with functional and therapeutic significance are shown. A blue circle indicates a missense mutation and a green circle indicates a silent mutation. The numbers in the circles represent the reported mutation numbers. The blue box indicates MAM domains and the pink box indicates the tyrosine kinase domain. b. Recurrent copy number (CN) gains in the 2p arm are defined by the MYCN locus on 2p24.3 and the ALK locus on 2p23, where vertical lines indicate common CN gains. High-grade amplifications are drawn in light red whereas simple gains are represented in dark red. c. Kinase activity of ALK mutants determined by in vitro kinase assays using the synthetic YFF peptide as a substrate.