Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes Journal Article
| Authors: | de la Fouchardière, A.; Tee, M. K.; Peternel, S.; Valdebran, M.; Pissaloux, D.; Tirode, F.; Busam, K. J.; LeBoit, P. E.; McCalmont, T. H.; Bastian, B. C.; Yeh, I. |
| Article Title: | Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes |
| Abstract: | A subset of Spitz tumors harbor fusions of NTRK3 with ETV6, MYO5A, and MYH9. We evaluated a series of 22 melanocytic tumors in which an NTRK3 fusion was identified as part of the diagnostic workup. Tumors in which NTRK3 was fused to ETV6 occurred in younger patients were predominantly composed of epithelioid melanocytes and were classified by their histopathologic features as Spitz tumors. In contrast, those in which NTRK3 was fused to MYO5A were predominantly composed of spindled melanocytes arrayed in fascicles with neuroid features such as pseudo-Verocay bodies. To further investigate the effects of the fusion kinases ETV6-NTRK3 and MYO5A-NTRK3 in melanocytes, we expressed them in immortalized melanocytes and determined their subcellular localization by immunofluorescence. ETV6-NTRK3 was localized to the nucleus and diffusely within the cytoplasm and caused melanocytes to adopt an epithelioid cytomorphology. In contrast, MYO5A-NTRK3, appeared excluded from the nucleus of melanocytes, was localized to dendrites, and resulted in a highly dendritic cytomorphology. Our findings indicate that ETV6-NTRK3 and MYO5A-NTRK3 have distinct subcellular localizations and effects on cellular morphology. © 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
| Keywords: | adult; child; clinical article; controlled study; human tissue; preschool child; school child; aged; young adult; unclassified drug; human cell; histopathology; lymph node dissection; sentinel lymph node biopsy; mitosis; phenotype; cell structure; basal cell carcinoma; melanocyte; immunofluorescence; protein tyrosine kinase; skin tumor; messenger rna; fusion gene; cellular distribution; cytoplasm; spitz nevus; cell nucleus; comparative genomic hybridization; hemangioma; chromosome 12p; xanthogranuloma; dendrite; verruca vulgaris; cyst; fusion protein; pyogenic granuloma; mastocytoma; pigmented nevus; human; male; female; priority journal; article; rna sequencing; pilomatrixoma; etv6 ntrk3 fusion protein; myo5a ntrk3 fusion protein; ntrk3 kinase |
| Journal Title: | Modern Pathology |
| Volume: | 34 |
| Issue: | 4 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2021-04-01 |
| Start Page: | 735 |
| End Page: | 747 |
| Language: | English |
| DOI: | 10.1038/s41379-020-00678-6 |
| PUBMED: | 32968185 |
| PROVIDER: | scopus |
| PMCID: | PMC7985048 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2021 -- Source: Scopus |
