Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion.

Autor:	Alsugair Z; Department of Pathology, Institut of Pathologie Multisite, Groupement Hospitalier Sud, Hospices Civils de Lyon., Perrot J; Department of Pathology, Institut of Pathologie Multisite, Groupement Hospitalier Sud, Hospices Civils de Lyon., Descotes F; Department of Biochemistry and Molecular Biology, Groupement Hospitalier Sud, Lyon, Pierre-Bénite., Lopez J; Department of Biochemistry and Molecular Biology, Groupement Hospitalier Sud, Lyon, Pierre-Bénite., Champagnac A; Department of Biopathology, Centre Léon Bérard., Pissaloux D; Department of Biopathology, Centre Léon Bérard.; The Unit of Molecular Pathology, INSERM, Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Université Claude Bernard Lyon 1., Castain C; Department of Oto-Rhino-Laryngology and Head and Neck Surgery, La Croix Rousse Hospital, Hospices Civils de Lyon., Onea M; EMR3738, CICLY, University Claude Bernard Lyon 1, Lyon., Céruse P; Department of Pathology, University Hospital of Bordeaux, Bordeaux., Philouze P; Department of Pathology, University Hospital of Bordeaux, Bordeaux., Lépine C; Department of Pathology, University Hospital of Strasbourg, Strasbourg.; Department of Pathology, CHU Nantes., Lanic MD; Nantes University, Univ Angers, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, Nantes.; INSERM U1245, Cancer Center Henri Becquerel, Institute of Research and Innovation in Biomedicine (IRIB), University of Normandy, UNIROUEN., Laé M; Nantes University, Univ Angers, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, Nantes.; INSERM U1245, Cancer Center Henri Becquerel, Institute of Research and Innovation in Biomedicine (IRIB), University of Normandy, UNIROUEN., Costes-Martineau V; Department of Pathology, Centre Henri Becquerel, Rouen., Benzerdjeb N; Department of Pathology, Institut of Pathologie Multisite, Groupement Hospitalier Sud, Hospices Civils de Lyon.; Department of Pathology, University Hospital of Montpellier, Montpellier, France.
Jazyk:	angličtina
Zdroj:	The American journal of surgical pathology [Am J Surg Pathol] 2024 May 01; Vol. 48 (5), pp. 551-561. Date of Electronic Publication: 2024 Mar 18.
DOI:	10.1097/PAS.0000000000002206
Abstrakt:	Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME. Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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