TY  - JOUR
AU  - Deng, Maximilian Y
AU  - Sill, Martin
AU  - Chiang, Jason
AU  - Schittenhelm, Jens
AU  - Ebinger, Martin
AU  - Schuhmann, Martin U
AU  - Monoranu, Camelia-Maria
AU  - Milde, Till
AU  - Wittmann, Andrea
AU  - Hartmann, Christian
AU  - Sommer, Clemens
AU  - Paulus, Werner
AU  - Gärtner, Jutta
AU  - Brück, Wolfgang
AU  - Rüdiger, Thomas
AU  - Leipold, Alfred
AU  - Jaunmuktane, Zane
AU  - Brandner, Sebastian
AU  - Giangaspero, Felice
AU  - Nozza, Paolo
AU  - Mora, Jaume
AU  - Morales la Madrid, Andres
AU  - Cruz Martinez, Ofelia
AU  - Hansford, Jordan R
AU  - Pietsch, Torsten
AU  - Tietze, Anna
AU  - Hernáiz-Driever, Pablo
AU  - Stoler, Iris
AU  - Capper, David
AU  - Korshunov, Andrey
AU  - Ellison, David W
AU  - von Deimling, Andreas
AU  - Pfister, Stefan
AU  - Sahm, Felix
AU  - Jones, David
TI  - Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features.
JO  - Acta neuropathologica
VL  - 136
IS  - 2
SN  - 1432-0533
CY  - Berlin
PB  - Springer
M1  - DKFZ-2018-01145
SP  - 239 - 253
PY  - 2018
AB  - Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80
LB  - PUB:(DE-HGF)16
C6  - pmid:29766299
DO  - DOI:10.1007/s00401-018-1865-4
UR  - https://inrepo02.dkfz.de/record/136677
ER  -