Figure 2: ROS1 fusions.
From: Kinase fusions are frequent in Spitz tumours and spitzoid melanomas
(a) Histological section of an atypical Spitz tumour with a PWWP2A–ROS1 fusion from the gluteal region of a 55-year-old female (haematoxylin and eosin stain). Scale bar, 500 μm. Scale bar magnification, 50 μm. (b) Immunohistochemistry for ROS1 shows expression in the melanocytes; stromal cells serve as internal negative controls. Scale bar, 500 μm. Scale bar magnification, 50 μm. The FISH inset confirms the gene rearrangements using breakpoint flanking FISH probes. The rearranged ROS1 locus appears as individual green and red signals, and the wild-type kinase allele with juxtaposed green/red signals. Scale bar, 10 μm. (c) Illustration of the PWWP2A–ROS1 kinase fusion. ROS1 is located on chromosome 1q21, and PWWP2A on chromosome 5q33. Owing to genomic rearrangements, exon 1 of PWWP2A is fused with exon 36–43 of ROS1, which contains the tyrosine kinase domain. The in-frame fusion junction of the transcript was confirmed by Sanger sequencing. (d) The PWWP2A–ROS1 fusion, but not the control-GFP construct, induces p-AKT, p-ERK, p-S6 and p-SHP2 in melan-a cells. Crizotinib inhibited at least partially the phosphorylation of the chimeric PWWP2A–ROS1 fusion protein, p-AKT, p-S6 and p-SHP2. The indicated protein weight markers in kDa are estimated from molecular weight standards. Results are representative of three independent experiments.
