000141128 001__ 141128 000141128 005__ 20240229105119.0 000141128 0247_ $$2doi$$a10.1038/s41379-018-0050-6 000141128 0247_ $$2pmid$$apmid:29802359 000141128 0247_ $$2ISSN$$a0893-3952 000141128 0247_ $$2ISSN$$a1530-0285 000141128 0247_ $$2altmetric$$aaltmetric:42614561 000141128 037__ $$aDKFZ-2018-01659 000141128 041__ $$aeng 000141128 082__ $$a610 000141128 1001_ $$aAppay, Romain$$b0 000141128 245__ $$aDuplications of KIAA1549 and BRAF screening by Droplet Digital PCR from formalin-fixed paraffin-embedded DNA is an accurate alternative for KIAA1549-BRAF fusion detection in pilocytic astrocytomas. 000141128 260__ $$aLondon$$bNature Publishing Group$$c2018 000141128 3367_ $$2DRIVER$$aarticle 000141128 3367_ $$2DataCite$$aOutput Types/Journal article 000141128 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1565682964_20521 000141128 3367_ $$2BibTeX$$aARTICLE 000141128 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000141128 3367_ $$00$$2EndNote$$aJournal Article 000141128 520__ $$aPilocytic astrocytomas represent the most common glioma subtype in young patients and account for 5.4% of all gliomas. They are characterized by alterations in the RAS-MAP kinase pathway, the most frequent being a tandem duplication on chromosome 7q34 involving the BRAF gene, resulting in oncogenic BRAF fusion proteins. BRAF fusion involving the KIAA1549 gene is a hallmark of pilocytic astrocytoma, but it has also been recorded in rare cases of gangliogliomas, 1p/19q co-deleted oligodendroglial tumors, and it is also a common feature of disseminated oligodendroglial-like leptomeningeal neoplasm. In some difficult cases, evidence for KIAA1549-BRAF fusion is of utmost importance for the diagnosis. Moreover, because the KIAA1549-BRAF fusion constitutively activates the MAP kinase pathway, it represents a target for drugs such as MEK inhibitors, and therefore, the detection of this genetic abnormality is highly relevant in the context of clinical trials applying such new approaches. In the present study, we aimed to use the high sensitivity of Droplet Digital PCR (DDPCR™) to predict KIAA1549-BRAF fusion on very small amounts of formalin-fixed paraffin-embedded tissue in routine practice. Therefore, we analyzed a training cohort of 55 pilocytic astrocytomas in which the KIAA1549-BRAF fusion status was known by RNA sequencing used as our gold standard technique. Then, we analyzed a prospective cohort of 40 pilocytic astrocytomas, 27 neuroepithelial tumors remaining difficult to classify (pilocytic astrocytoma versus ganglioglioma or diffuse glioma), 15 dysembryoplastic neuroepithelial tumors, and 18 gangliogliomas. We could demonstrate the usefulness and high accuracy (100% sensitivity and specificity when compared to RNA sequencing) of DDPCR™ to assess the KIAA1549-BRAF fusion from very low amounts of DNA isolated from formalin-fixed paraffin-embedded specimens. BRAF duplication is both necessary and sufficient to predict this fusion in most cases and we propose that this single analysis could be used in routine practice to save time, money, and precious tissue. 000141128 536__ $$0G:(DE-HGF)POF3-319H$$a319H - Addenda (POF3-319H)$$cPOF3-319H$$fPOF III$$x0 000141128 588__ $$aDataset connected to CrossRef, PubMed, 000141128 7001_ $$aFina, Frédéric$$b1 000141128 7001_ $$00000-0002-9882-2162$$aMacagno, Nicolas$$b2 000141128 7001_ $$aPadovani, Laëtitia$$b3 000141128 7001_ $$aColin, Carole$$b4 000141128 7001_ $$aBarets, Doriane$$b5 000141128 7001_ $$aOrdioni, Joanna$$b6 000141128 7001_ $$aScavarda, Didier$$b7 000141128 7001_ $$aGiangaspero, Felice$$b8 000141128 7001_ $$aBadiali, Manuela$$b9 000141128 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b10$$udkfz 000141128 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b11$$udkfz 000141128 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b12$$udkfz 000141128 7001_ $$aFigarella-Branger, Dominique$$b13 000141128 773__ $$0PERI:(DE-600)2041318-X$$a10.1038/s41379-018-0050-6$$gVol. 31, no. 10, p. 1490 - 1501$$n10$$p1490 - 1501$$tModern pathology$$v31$$x1530-0285$$y2018 000141128 909CO $$ooai:inrepo02.dkfz.de:141128$$pVDB 000141128 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ 000141128 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ 000141128 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ 000141128 9131_ $$0G:(DE-HGF)POF3-319H$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vAddenda$$x0 000141128 9141_ $$y2018 000141128 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bMODERN PATHOL : 2017 000141128 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000141128 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000141128 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000141128 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000141128 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000141128 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000141128 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000141128 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine 000141128 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000141128 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000141128 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bMODERN PATHOL : 2017 000141128 9201_ $$0I:(DE-He78)G380-20160331$$kG380$$lKKE Neuropathologie$$x0 000141128 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lPädiatrische Neuroonkologie$$x1 000141128 9201_ $$0I:(DE-He78)L101-20160331$$kL101$$lDKTK Heidelberg$$x2 000141128 980__ $$ajournal 000141128 980__ $$aVDB 000141128 980__ $$aI:(DE-He78)G380-20160331 000141128 980__ $$aI:(DE-He78)B062-20160331 000141128 980__ $$aI:(DE-He78)L101-20160331 000141128 980__ $$aUNRESTRICTED