A Novel Fusion Partner, SP100, Drives Nuclear Dot Localization of ALK in Epithelioid Fibrous Histiocytoma.
Am J Dermatopathol
; 45(8): 539-543, 2023 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-37377191
ABSTRACT
ABSTRACT Epithelioid fibrous histiocytoma (EFH) is a distinctive benign cutaneous neoplasm composed of uniform epithelioid cells, often with binucleated cells. EFH are characterized by the presence of anaplastic lymphoma kinase ( ALK ) gene rearrangements with a variety of binding partners. These rearrangements result in the overexpression of ALK , which can be detected using immunohistochemistry. Cytoplasmic ALK expression is by far the most common pattern encountered. Here, we describe a case of EFH with a distinctive intranuclear dot-like ALK expression pattern. Subsequent next-generation DNA sequencing revealed a novel SP100ALK gene fusion. Speckled protein-100 (SP100) is a constituent of nuclear dots, also known as promyelocytic leukemia bodies, which are still poorly understood membraneless subnuclear structures. Thus, this novel ALK fusion partner seems to explain this distinctive pattern of ALK localization. We examined ALK expression patterns in 11 other cases of EFH, but all showed typical cytoplasmic localization. This study expands the morphologic and molecular spectrum of EFH, provides a dramatic illustration of the ability of fusion partners to control protein localization, and implies that tumorigenic ALK signaling may occur at a variety of subcellular locations.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Histiocitoma Fibroso Benigno
Límite:
Humans
Idioma:
En
Revista:
Am J Dermatopathol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Marruecos