RESUMEN
BACKGROUND/AIM: Gliomas are primary malignancies of the central nervous system (CNS). High-grade gliomas are associated with poor prognosis and modest survival rates despite intensive multimodal treatment strategies. Targeting gene fusions is an emerging therapeutic approach for gliomas that allows application of personalized medicine principles. The aim of this study was to identify detectable fusion oncogenes that could serve as predictors of currently available or newly developed targeted therapeutics in cross-sectional samples from glioma patients using next-generation sequencing (NGS). PATIENTS AND METHODS: A total of 637 patients with glial and glioneuronal tumours of the CNS who underwent tumour resection between 2017 and 2020 were enrolled. Detection of fusion transcripts in FFPE tumour tissue was performed by a TruSight Tumour 170 assay and two FusionPlex kits, Solid Tumour and Comprehensive Thyroid and Lung. RESULTS: Oncogene fusions were identified in 33 patients. The most common fusion was the KIAA1549-BRAF fusion, detected in 13 patients, followed by FGFR fusions (FGFR1-TACC1, FGFR2-CTNNA3, FGFR3-TACC3, FGFR3-CKAP5, FGFR3-AMBRA1), identified in 10 patients. Other oncogene fusions were also infrequently diagnosed, including MET fusions (SRPK2-MET and PTPRZ1-MET) in 2 patients, C11orf95-RELA fusions in 2 patients, EGFR-SEPT14 fusion in 2 patients, and individual cases of SRGAP3-BRAF, RAF1-TRIM2, EWSR1-PALGL1 and TERT-ALK fusions. CONCLUSION: The introduction of NGS techniques provides additional information about tumour molecular alterations that can aid the multimodal management of glioma patients. Patients with gliomas positive for particular targetable gene fusions may benefit from experimental therapeutics, enhancing their quality of life and prolonging survival rates.
Asunto(s)
Glioma , Fusión de Oncogenes , Proteínas Adaptadoras Transductoras de Señales/genética , Estudios Transversales , Glioma/genética , Glioma/patología , Humanos , Proteínas Asociadas a Microtúbulos/genética , Oncogenes/genética , Proteínas Serina-Treonina Quinasas , Calidad de Vida , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/genéticaRESUMEN
The 14-3-3 family proteins are phosphoserine/phosphothreonine binding proteins constituting a conserved class of proteins which are detected in all eukaryotic cells. In mammalians, 14-3-3 proteins have seven distinct isoforms (ß, γ, ε, η, ζ, σ and τ/θ) which are involved in various cellular processes including signal transduction, cell cycle, cell proliferation, apoptosis, differentiation and survival. 14-3-3 proteins do not have a distinct catalytic activity and often regulate the activity, stability, subcellular localization and interactions of other proteins. The 14-3-3 family proteins function through interacting with their client proteins or facilitating the interaction of other proteins likely as adaptor proteins. The versatile functions of these proteins in the regulation of cell growth, cell division, cell death and cell migration make them candidate proteins for which an important role in cancer development could be envisioned. Indeed, analysis of cancer cell lines and tumor-derived tissues have indicated the differential abundance or post-translational modification of some 14-3-3 isoforms. In this review, we aimed to show how deregulation of 14-3-3 proteins contributes to initiation, establishment and progression of cancers with a particular emphasis on lung cancer. The role of these proteins in cancer-relevant processes including cell cycle, cell migration, cell-cell communication and programmed cell death will be discussed in detail.