Figure 4: NTRK1 fusions.
From: Kinase fusions are frequent in Spitz tumours and spitzoid melanomas
(a) Histological section of a spitzoid melanoma with a LMNA–NTRK1 fusion excised from the left knee of a 39-year-old woman (haematoxylin and eosin stain). Scale bar, 500 μm. Scale bar magnification, 50 μm. (b) Immunohistochemistry demonstrates the NTRK1 expression in 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 by the individual green and red signals. Scale bar, 10 μm. (c) The LMNA–NTRK1 kinase fusion is caused by a 743 kb deletion on chromosome 1q, joining the first two exons of LMNA with exon 11–17 of NTRK1. The in-frame junction of the fusion transcript was confirmed with Sanger sequencing. (d) The LMNA–NTRK1 fusion construct, but not the full-length, wild-type NTRK1 or the control-GFP constructs induce p-AKT, p-ERK, p-S6 and p-PLCγ1 in melan-a cells. A small molecule kinase inhibitor, AZ-23, inhibited the phosphorylation of LMNA–NTRK1 and the activation of the oncogenic signalling pathways. The indicated protein weight markers in kDa are estimated from molecular weight standards. Results are representative of three independent experiments.
