000144235 001__ 144235 000144235 005__ 20240229112619.0 000144235 0247_ $$2doi$$a10.1007/s00401-019-02039-3 000144235 0247_ $$2pmid$$apmid:31278449 000144235 0247_ $$2ISSN$$a0001-6322 000144235 0247_ $$2ISSN$$a1432-0533 000144235 0247_ $$2altmetric$$aaltmetric:63241441 000144235 037__ $$aDKFZ-2019-01755 000144235 041__ $$aeng 000144235 082__ $$a610 000144235 1001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b0$$eFirst author 000144235 245__ $$aRoutine RNA sequencing of formalin-fixed paraffin-embedded specimens in neuropathology diagnostics identifies diagnostically and therapeutically relevant gene fusions. 000144235 260__ $$aHeidelberg$$bSpringer$$c2019 000144235 3367_ $$2DRIVER$$aarticle 000144235 3367_ $$2DataCite$$aOutput Types/Journal article 000144235 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1631629415_29203 000144235 3367_ $$2BibTeX$$aARTICLE 000144235 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000144235 3367_ $$00$$2EndNote$$aJournal Article 000144235 520__ $$aMolecular markers have become pivotal in brain tumor diagnostics. Mutational analyses by targeted next-generation sequencing of DNA and array-based DNA methylation assessment with copy number analyses are increasingly being used in routine diagnostics. However, the broad variety of gene fusions occurring in brain tumors is marginally covered by these technologies and often only assessed by targeted assays. Here, we assessed the feasibility and clinical value of investigating gene fusions in formalin-fixed paraffin-embedded (FFPE) tumor tissues by next-generation mRNA sequencing in a routine diagnostic setting. After establishment and optimization of a workflow applicable in a routine setting, prospective diagnostic application in a neuropathology department for 26 months yielded relevant fusions in 66 out of 101 (65%) analyzed cases. In 43 (43%) cases, the fusions were of decisive diagnostic relevance and in 40 (40%) cases the fusion genes rendered a druggable target. A major strength of this approach was its ability to detect fusions beyond the canonical alterations for a given entity, and the unbiased search for any fusion event in cases with uncertain diagnosis and, thus, uncertain spectrum of expected fusions. This included both rare variants of established fusions which had evaded prior targeted analyses as well as the detection of previously unreported fusion events. While the impact of fusion detection on diagnostics is highly relevant, it is especially the detection of 'druggable' fusions which will most likely provide direct benefit to the patients. The wider application of this approach for unbiased fusion identification therefore promises to be a major advance in identifying alterations with immediate impact on patient care. 000144235 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000144235 588__ $$aDataset connected to CrossRef, PubMed, 000144235 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b1 000144235 7001_ $$0P:(DE-HGF)0$$aCasalini, Belén$$b2 000144235 7001_ $$0P:(DE-He78)b6273c0ba3ae37a4d3d1c6b084797f2e$$aMeyer, Jochen$$b3 000144235 7001_ $$0P:(DE-HGF)0$$aWefers, Annika K$$b4 000144235 7001_ $$0P:(DE-HGF)0$$aSievers, Philipp$$b5 000144235 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b6 000144235 7001_ $$0P:(DE-HGF)0$$aKoelsche, Christian$$b7 000144235 7001_ $$0P:(DE-HGF)0$$aReuss, David E$$b8 000144235 7001_ $$0P:(DE-HGF)0$$aReinhardt, Annekathrin$$b9 000144235 7001_ $$0P:(DE-HGF)0$$aEbrahimi, Azadeh$$b10 000144235 7001_ $$0P:(DE-HGF)0$$aFernández-Klett, Francisco$$b11 000144235 7001_ $$0P:(DE-He78)5c2c9cbe6ce72553684d82d94aebdadd$$aKessler, Tobias$$b12 000144235 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b13 000144235 7001_ $$0P:(DE-He78)3de637452ba900e2bdd359b8f41953bf$$aEcker, Jonas$$b14 000144235 7001_ $$0P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aMilde, Till$$b15 000144235 7001_ $$aHerold-Mende, Christel$$b16 000144235 7001_ $$0P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aWitt, Olaf$$b17 000144235 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b18 000144235 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b19 000144235 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b20 000144235 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b21$$eLast author 000144235 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b22$$eLast author 000144235 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