CARMN-NOTCH2 fusion transcript drives high NOTCH2 expression in glomus tumors of the upper digestive tract.

Autor: Girard N; EA4340 Research Unit, University of Versailles SQY, Boulogne, France., Marin C; EA4340 Research Unit, University of Versailles SQY, Boulogne, France.; Department of Pathology, Ambroise Paré Hospital, Boulogne, France., Hélias-Rodzewicz Z; EA4340 Research Unit, University of Versailles SQY, Boulogne, France.; Department of Pathology, Ambroise Paré Hospital, Boulogne, France., Villa C; Department of Pathology, Foch Hospital, Suresnes, France., Julié C; EA4340 Research Unit, University of Versailles SQY, Boulogne, France.; Department of Pathology, Ambroise Paré Hospital, Boulogne, France., de Lajarte-Thirouard AS; Department of Pathology, Centre Hospitalier Universitaire de Pontchaillou, Rennes, France., de Beauce SM; Department of Pathology, Centre Hospitalier de Valenciennes, Valenciennes, France., Lagorce-Pages C; INSERM UMRS1138 Unit, Centre de Recherche des Cordeliers, Paris, France.; University of Paris Descartes, Paris, France.; Department of Pathology, Georges Pompidou European Hospital, Paris, France., Renaud F; University of Lille Nord de France, Lille, France.; INSERM, UMR-S 1172 Unit, Lille, France.; Department of Pathology, Lille University Hospital, Lille, France., Cazals-Hatem D; University Hospital Department (DHU) UNITY, Beaujon Hospital, Clichy, France.; Inflammation Research Center (CRI), UMR 1149 Unit, University of Paris Diderot and INSERM, Paris, France.; Department of Pathology, Beaujon Hospital, Clichy, France., Guedj N; University Hospital Department (DHU) UNITY, Beaujon Hospital, Clichy, France.; Inflammation Research Center (CRI), UMR 1149 Unit, University of Paris Diderot and INSERM, Paris, France.; Department of Pathology, Beaujon Hospital, Clichy, France., Cros J; University Hospital Department (DHU) UNITY, Beaujon Hospital, Clichy, France.; Inflammation Research Center (CRI), UMR 1149 Unit, University of Paris Diderot and INSERM, Paris, France.; Department of Pathology, Beaujon Hospital, Clichy, France., Raffin-Sanson ML; Endocrinology and Nutrition Department, Ambroise Paré Hospital, Boulogne, France.; INSERM U1173 Unit, University of Versailles SQY, Montigny-le-Bretonneux, France., Selves J; Department of Pathology, Oncopole, Toulouse, France., Terris B; INSERM, U1016 Unit, Cochin Institute, Paris, France.; CNRS, UMR8104 Unit, University of Paris Descartes, Paris, France.; Department of Pathology, Cochin Institute, Paris, France., Fléjou JF; Department of Pathology, Saint-Antoine Hospital, Paris, France., Garchon HJ; INSERM U1173 Unit, University of Versailles SQY, Montigny-le-Bretonneux, France.; Faculty of Health Sciences Simone Veil, University of Versailles SQY, Montigny-le-Bretonneux, France., Coindre JM; Department of Pathology, Bergonié Institute, Bordeaux, France.; INSERM U916 Unit, Bergonié Institute, Bordeaux, France.; Department of Pathology, University of Victor Segalen, Bordeaux, France., Emile JF; EA4340 Research Unit, University of Versailles SQY, Boulogne, France.; Department of Pathology, Ambroise Paré Hospital, Boulogne, France.
Jazyk: angličtina
Zdroj: Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2021 Nov; Vol. 60 (11), pp. 723-732. Date of Electronic Publication: 2021 Jul 21.
DOI: 10.1002/gcc.22981
Abstrakt: Glomus tumors (GTs) are perivascular tumors mostly occurring in the distal extremities. Rare cases arise in the digestive tract and may be misdiagnosed with neuroendocrine or gastrointestinal stromal tumors. We aimed to specify the features of GT of the upper digestive tract. Clinical, histological, phenotypic, and molecular features of 16 digestive GTs were analyzed, of whom two underwent whole exome and RNA sequencing to search for gene alterations. RNA-sequencing disclosed a t(1:5)(p13;q32) translocation, which resulted in the fusion of CARMN and NOTCH2 in two GTs. The fusion gene encoded a protein sequence corresponding to the NOTCH2 intracellular domain that functions as transcription factor. These finding was supported by high expression of genes targeted by NOTCH. The CARMN-NOTCH2 translocation was detected in 14 out of 16 (88%) GTs of the upper digestive tract; but in only in two out of six cutaneous GTs (33%). Most digestive GT arose from the stomach (n = 13), and the others from duodenal (2) or oesophagous (1). Nuclear expression of NOTCH2 was detected in the 14 cases containing the fusion transcripts. The CARMN-NOTCH2 fusion transcript may contribute to activation of the NOTCH2 pathway in GT and drive tumor development. The high frequency of this translocation in GT of the upper digestive track suggest that detection of nuclear NOTCH2 expression may be useful diagnostic biomarker of these tumors.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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