Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes

Autor: Iwei Yeh, Timothy H. McCalmont, Meng Kian Tee, Arnaud de la Fouchardière, Boris C. Bastian, Philip E. LeBoit, Franck Tirode, Sandra Peternel, Daniel Pissaloux, Klaus J. Busam, Manuel Valdebran
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Pathology
Melanoma
Spitz nevus
Gene fusion
NTRK3 protein
Myo5a protein
Tyrosine kinase
Skin Neoplasms
Oncogene Proteins
Fusion
Medical and Health Sciences
0302 clinical medicine
Child
Cancer
Oncogene Proteins
Tumor
medicine.diagnostic_test
Kinase
Middle Aged
medicine.anatomical_structure
Phenotype
030220 oncology & carcinogenesis
Child
Preschool
trkC
Melanocytes
Female
Gene Fusion
Receptor
Adult
medicine.medical_specialty
Adolescent
Myosin Type V
Epithelioid and Spindle Cell
Biology
Immunofluorescence
Article
Pathology and Forensic Medicine
Cell Line
03 medical and health sciences
Young Adult
Nevus
Epithelioid and Spindle Cell
medicine
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
Receptor
trkC
Fusion
Preschool
Nevus
Cell Shape
Aged
Myosin Heavy Chains
Extramural
Subcellular localization
ETV6
030104 developmental biology
Cytoplasm
Cellular Morphology
Nucleus
Biomarkers
Zdroj: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, vol 34, iss 4
ISSN: 1530-0285
Popis: 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.
Databáze: OpenAIRE
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