Frequency and functional characterization of fusion genes in squamous cell carcinoma of the lung.

Autor: Alidousty C; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany; Network Genomic Medicine, Cologne, Germany., Becker A; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany., Binot E; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany., Hillmer AM; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany; Network Genomic Medicine, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Robert Koch Strasse 21, 50931 Cologne, Germany., Merkelbach-Bruse S; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany; Network Genomic Medicine, Cologne, Germany., Budde B; Cologne Center for Genomics, Medical Faculty of the University of Cologne, Weyertal 115b, 50931 Cologne, Germany., Bäßmann I; Cologne Center for Genomics, Medical Faculty of the University of Cologne, Weyertal 115b, 50931 Cologne, Germany., Rappl G; Center for Molecular Medicine Cologne, University of Cologne, Robert Koch Strasse 21, 50931 Cologne, Germany., Wolf J; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital Cologne, Cologne, Germany., Eich ML; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany., Noh KW; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany., Buettner R; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany; Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital Cologne, Cologne, Germany., Schultheis AM; University Hospital and Medical Faculty, University of Cologne, Institute of Pathology, Kerpener Straße 62, 50937 Cologne, Germany. Electronic address: anne.schultheis@uk-koeln.de.
Jazyk: angličtina
Zdroj: Gene [Gene] 2024 Feb 15; Vol. 895, pp. 148018. Date of Electronic Publication: 2023 Nov 18.
DOI: 10.1016/j.gene.2023.148018
Abstrakt: Introduction: In contrast to lung adenocarcinoma (LUAD), targetable genetic alterations are less frequently detected in squamous cell carcinoma of the lung (LUSC). Over the last years, gene fusions have become promising targets in many solid cancers. Here, we analysed a cohort of LUSC, identified recurrent fusion genes and functionally characterised these tumour genomes.
Methods: A subset of 1608 squamous cell carcinomas of the lung was analysed by means of the FusionPlex® Lung Panel to identify potentially targetable gene fusions using targeted next-generation sequencing. Cases harbouring recurrent gene fusions were further analysed using FISH, Cytoscan HD arrays and cell culture experiments.
Results: We found both, known and novel gene fusions in about 3 % of the cases. Known fusions occurring in lung cancer included ALK::EML4, EGFRvIII, EZR::ROS1 and FGFR3::TACC. We further identified recurrent gene fusions of currently unknown biological function, involving EGFR::VSTM2A and NSD3::FGFR1 and showed that the occurrence of the EGFR::VSTM2A fusion is accompanied by high-level amplification of EGFR. Our analyses further revealed that the genomes of these LUSC patients are chromosomally unstable, which leads us to believe that such non-actionable genomic rearrangements may be a result of "chromosomal chaos" most probably not representing exclusive cancer-driving genes in this cancer entity.
Conclusions: We emphasise that caution should be taken when novel fusions are found and that the appearance of new gene fusions should always be interpreted in the molecular context of the respective disease.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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