Figure 3: ALK fusions.
From: Kinase fusions are frequent in Spitz tumours and spitzoid melanomas
(a) Histological section of an atypical Spitz tumour with a DCTN1–ALK fusion excised from the upper arm of a 19-year-old male (haematoxylin and eosin stain). Scale bar, 500 μm. Scale bar magnification, 50 μm. (b) Immunohistochemistry shows ALK expression in the melanocytes; stromal cells serve as internal negative controls. Scale bar, 500 μm. Scale bar magnification, 50 μm. (c) FISH demonstrates the ALK gene rearrangement by the individual green and orange signals using breakpoint flanking probes. Scale bar, 10 μm. (d) Illustration of the DCTN1–ALK kinase fusion. ALK is located on chromosome 2p23 and DCTN1 on chromosome 2p13. Owing to genomic rearrangements, exon 1–26 of DCTN1 is fused with exon 20–29 of ALK, which contains the tyrosine kinase domain. The in-frame junction of the fusion transcript was confirmed with Sanger sequencing. (e) The DCTN1–ALK fusion construct, but not the control-GFP construct, induces p-AKT, p-ERK and p-S6 in melan-a cells. These effects and the phosphorylation of chimeric DCTN1–ALK protein can be inhibited with crizotinib. The indicated protein weight markers in kDa are estimated from molecular weight standards. Results are representative of three independent experiments.
