TY  - JOUR
AU  - Rivera, Barbara
AU  - Gayden, Tenzin
AU  - Carrot-Zhang, Jian
AU  - Nadaf, Javad
AU  - Boshari, Talia
AU  - Faury, Damien
AU  - Zeinieh, Michele
AU  - Blanc, Romeo
AU  - Burk, David L
AU  - Fahiminiya, Somayyeh
AU  - Bareke, Eric
AU  - Schüller, Ulrich
AU  - Monoranu, Camelia M
AU  - Sträter, Ronald
AU  - Kerl, Kornelius
AU  - Niederstadt, Thomas
AU  - Kurlemann, Gerhard
AU  - Ellezam, Benjamin
AU  - Michalak, Zuzanna
AU  - Thom, Maria
AU  - Lockhart, Paul J
AU  - Leventer, Richard J
AU  - Ohm, Milou
AU  - MacGregor, Duncan
AU  - Jones, David
AU  - Karamchandani, Jason
AU  - Greenwood, Celia M T
AU  - Berghuis, Albert M
AU  - Bens, Susanne
AU  - Siebert, Reiner
AU  - Zakrzewska, Magdalena
AU  - Liberski, Pawel P
AU  - Zakrzewski, Krzysztof
AU  - Sisodiya, Sanjay M
AU  - Paulus, Werner
AU  - Albrecht, Steffen
AU  - Hasselblatt, Martin
AU  - Jabado, Nada
AU  - Foulkes, William D
AU  - Majewski, Jacek
TI  - Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors.
JO  - Acta neuropathologica
VL  - 131
IS  - 6
SN  - 1432-0533
CY  - Berlin
PB  - Springer
M1  - DKFZ-2017-05497
SP  - 847 - 863
PY  - 2016
AB  - 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 
KW  - FGFR1 protein, human (NLM Chemicals)
KW  - Receptor, Fibroblast Growth Factor, Type 1 (NLM Chemicals)
KW  - Proto-Oncogene Proteins B-raf (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26920151
C2  - pmc:PMC5039033
DO  - DOI:10.1007/s00401-016-1549-x
UR  - https://inrepo02.dkfz.de/record/130418
ER  -