%0 Journal Article
%A Rivera, Barbara
%A Gayden, Tenzin
%A Carrot-Zhang, Jian
%A Nadaf, Javad
%A Boshari, Talia
%A Faury, Damien
%A Zeinieh, Michele
%A Blanc, Romeo
%A Burk, David L
%A Fahiminiya, Somayyeh
%A Bareke, Eric
%A Schüller, Ulrich
%A Monoranu, Camelia M
%A Sträter, Ronald
%A Kerl, Kornelius
%A Niederstadt, Thomas
%A Kurlemann, Gerhard
%A Ellezam, Benjamin
%A Michalak, Zuzanna
%A Thom, Maria
%A Lockhart, Paul J
%A Leventer, Richard J
%A Ohm, Milou
%A MacGregor, Duncan
%A Jones, David
%A Karamchandani, Jason
%A Greenwood, Celia M T
%A Berghuis, Albert M
%A Bens, Susanne
%A Siebert, Reiner
%A Zakrzewska, Magdalena
%A Liberski, Pawel P
%A Zakrzewski, Krzysztof
%A Sisodiya, Sanjay M
%A Paulus, Werner
%A Albrecht, Steffen
%A Hasselblatt, Martin
%A Jabado, Nada
%A Foulkes, William D
%A Majewski, Jacek
%T Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors.
%J Acta neuropathologica
%V 131
%N 6
%@ 1432-0533
%C Berlin
%I Springer
%M DKFZ-2017-05497
%P 847 - 863
%D 2016
%X Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor associated with intractable drug-resistant epilepsy. In order to identify underlying genetic alterations and molecular mechanisms, we examined three family members affected by multinodular DNETs as well as 100 sporadic tumors from 96 patients, which had been referred to us as DNETs. We performed whole-exome sequencing on 46 tumors and targeted sequencing for hotspot FGFR1 mutations and BRAF p.V600E was used on the remaining samples. FISH, copy number variation assays and Sanger sequencing were used to validate the findings. By whole-exome sequencing of the familial cases, we identified a novel germline FGFR1 mutation, p.R661P. Somatic activating FGFR1 mutations (p.N546K or p.K656E) were observed in the tumor samples and further evidence for functional relevance was obtained by in silico modeling. The FGFR1 p.K656E mutation was confirmed to be in cis with the germline p.R661P variant. In 43 sporadic cases, in which the diagnosis of DNET could be confirmed on central blinded neuropathology review, FGFR1 alterations were also frequent and mainly comprised intragenic tyrosine kinase FGFR1 duplication and multiple mutants in cis (25/43; 58.1 
%K FGFR1 protein, human (NLM Chemicals)
%K Receptor, Fibroblast Growth Factor, Type 1 (NLM Chemicals)
%K Proto-Oncogene Proteins B-raf (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26920151
%2 pmc:PMC5039033
%R 10.1007/s00401-016-1549-x
%U https://inrepo02.dkfz.de/record/130418