%0 Journal Article
%A Snuderl, Matija
%A Kannan, Kasthuri
%A Pfaff, Elke
%A Wang, Shiyang
%A Stafford, James M
%A Serrano, Jonathan
%A Heguy, Adriana
%A Ray, Karina
%A Faustin, Arline
%A Aminova, Olga
%A Dolgalev, Igor
%A Stapleton, Stacie L
%A Zagzag, David
%A Chiriboga, Luis
%A Gardner, Sharon L
%A Wisoff, Jeffrey H
%A Golfinos, John G
%A Capper, David
%A Hovestadt, Volker
%A Rosenblum, Marc K
%A Placantonakis, Dimitris G
%A LeBoeuf, Sarah E
%A Papagiannakopoulos, Thales Y
%A Chavez, Lukas
%A Ahsan, Sama
%A Eberhart, Charles G
%A Pfister, Stefan
%A Jones, David
%A Karajannis, Matthias A
%T Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma.
%J Nature Communications
%V 9
%N 1
%@ 2041-1723
%C London
%I Nature Publishing Group
%M DKFZ-2018-01252
%P 2868
%D 2018
%X Pineoblastoma is a rare and highly aggressive brain cancer of childhood, histologically belonging to the spectrum of primitive neuroectodermal tumors. Patients with germline mutations in DICER1, a ribonuclease involved in microRNA processing, have increased risk of pineoblastoma, but genetic drivers of sporadic pineoblastoma remain unknown. Here, we analyzed pediatric and adult pineoblastoma samples (n = 23) using a combination of genome-wide DNA methylation profiling and whole-exome sequencing or whole-genome sequencing. Pediatric and adult pineoblastomas showed distinct methylation profiles, the latter clustering with lower-grade pineal tumors and normal pineal gland. Recurrent variants were found in genes involved in PKA- and NF-κB signaling, as well as in chromatin remodeling genes. We identified recurrent homozygous deletions of DROSHA, acting upstream of DICER1 in microRNA processing, and a novel microduplication involving chromosomal region 1q21 containing PDE4DIP (myomegalin), comprising the ancient DUF1220 protein domain. Expresion of PDE4DIP and DUF1220 proteins was present exclusively in pineoblastoma with PDE4DIP gain.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30030436
%2 pmc:PMC6054684
%R 10.1038/s41467-018-05029-3
%U https://inrepo02.dkfz.de/record/136814