Hernandez, AinhoaMuñoz-Mármol, Ana M.Esteve-Codina, AnnaAlameda Quitllet, FranciscoCarrato, CristinaPineda, EstelaArpí Llucià, OriolMartinez-García, MariaMallo, MarGut, MartaBarco Berrón, Sonia delGallego, OscarDabad, MarcMesia, CarlosBellosillo Paricio, BeatrizDomenech, MartaVidal, NoemíAldecoa, IbanIglesia, Nuria de laBalana, Carmen2022-11-092022-11-092022Hernandez A, Muñoz-Mármol AM, Esteve-Codina A, Alameda F, Carrato C, Pineda E, Arpí-Lluciá O, Martinez-García M, Mallo M, Gut M, Del Barco S, Gallego O, Dabad M, Mesia C, Bellosillo B, Domenech M, Vidal N, Aldecoa I, de la Iglesia N, Balana C. In silico validation of RNA-Seq results can identify gene fusions with oncogenic potential in glioblastoma. Sci Rep. 2022 Aug 24;12(1):14439. DOI: 10.1038/s41598-022-18608-82045-2322http://hdl.handle.net/10230/54767RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have functional consequences. Using multiple data bases, we have performed an in silico analysis of fusions detected by RNA-Seq in tumor samples from 139 newly diagnosed glioblastoma patients to identify in-frame fusions with predictable oncogenic potential. Among 61 samples with fusions, there were 103 different fusions, involving 167 different genes, including 20 known oncogenes or tumor suppressor genes (TSGs), 16 associated with cancer but not oncogenes or TSGs, and 32 not associated with cancer but previously shown to be involved in fusions in gliomas. After selecting in-frame fusions able to produce a protein product and running Oncofuse, we identified 30 fusions with predictable oncogenic potential and classified them into four non-overlapping categories: six previously described in cancer; six involving an oncogene or TSG; four predicted by Oncofuse to have oncogenic potential; and 14 other in-frame fusions. Only 24 patients harbored one or more of these 30 fusions, and only two fusions were present in more than one patient: FGFR3::TACC3 and EGFR::SEPTIN14. This in silico study provides a good starting point for the identification of gene fusions with functional consequences in the pathogenesis or treatment of glioblastoma.application/pdfeng© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-022-18608-8CancerCNS cancerMolecular biologyMolecular neuroscienceNeuroscienceinfo:eu-repo/semantics/openAccess