Figure 5: RET fusions.

(a) Histological section of a pigmented spindle cell naevus (a morphological variant of Spitz naevus) with a GOLGA5–RET fusion excised from a 50-year-old woman (haematoxylin and eosin stain). Scale bar, 500 μm. Scale bar magnification, 50 μm. (b) RET expression in melanocytes; keratinocytes serve as internal negative controls. Scale bar, 100 μm. The individual green and red signals in FISH confirm the gene rearrangements using breakpoint flanking FISH probes. Scale bar, 10 μm. (c,d) The GOLGA5–RET construct, but not the wild-type, full-length RET or the control-GFP constructs induces p-AKT, p-ERK, p-S6 and p-PLCγ1 in melan-a cells. The activation of these pathways and the phosphorylation of GOLGA5–RET can be inhibited with (c) vandetanib and (d) cabozantinib. The indicated protein weight markers in kDa are estimated from molecular weight standards. Results are representative of three independent experiments.