Fig. 3: Functional and structural characteristics of ALK alterations associated with FUS/EWSR1-TFCP2 RMS.
a Colony formation of MCF10A cells stably transduced with ALK alterations or EV. Mean ± SEM (n = 3 independent experiments). b Anchorage-independent growth in soft agar of MCF10A cells stably transduced with ALK alterations or EV. Mean ± SEM (n = 3 independent experiments). c Tumor growth in NOD-SCID mice of MCF10A cells stably transduced with ALK alterations or EV. Shown is the mean volume ± SEM of six tumors per cell line until the first mouse had to be sacrificed in one group due to reaching the maximum allowed tumor length. d Sensitivity of MCF10A cells stably transduced with the indicated ALK variants or EV to crizotinib, ceritinib, or alectinib after 72 h in the absence of EGF. Drug concentrations (conc.) are shown at the top of the heatmap. Mean cell viability of drug-treated cells relative to the respective DMSO control (n = 2 independent experiments). e Sensitivity of freshly isolated and singularized cells from tumor sample TFCP2-HD-4 to the ALK inhibitors crizotinib, ceritinib, or alectinib. Vertical dotted lines represent the Cmax of each compound. Mean ± SEM (n = 4 technical replicates). f Domain architectures of ALK variants. Pairings between cysteines in each variant are indicated by red lines. SP signal peptide, MAM meprin A-5 protein, and receptor protein-tyrosine phosphatase mu domain, LDL low-density lipoprotein receptor class A, EGF epidermal growth factor-like domain, TM transmembrane helix, Pkinase_tyr tyrosine protein kinase domain. Statistical significance was assessed by a one-tailed unpaired t-test. ns not significant. Source data for a–e are provided in the Source Data file.
