TY  - JOUR
AU  - Snuderl, Matija
AU  - Kannan, Kasthuri
AU  - Pfaff, Elke
AU  - Wang, Shiyang
AU  - Stafford, James M
AU  - Serrano, Jonathan
AU  - Heguy, Adriana
AU  - Ray, Karina
AU  - Faustin, Arline
AU  - Aminova, Olga
AU  - Dolgalev, Igor
AU  - Stapleton, Stacie L
AU  - Zagzag, David
AU  - Chiriboga, Luis
AU  - Gardner, Sharon L
AU  - Wisoff, Jeffrey H
AU  - Golfinos, John G
AU  - Capper, David
AU  - Hovestadt, Volker
AU  - Rosenblum, Marc K
AU  - Placantonakis, Dimitris G
AU  - LeBoeuf, Sarah E
AU  - Papagiannakopoulos, Thales Y
AU  - Chavez, Lukas
AU  - Ahsan, Sama
AU  - Eberhart, Charles G
AU  - Pfister, Stefan
AU  - Jones, David
AU  - Karajannis, Matthias A
TI  - Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma.
JO  - Nature Communications
VL  - 9
IS  - 1
SN  - 2041-1723
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2018-01252
SP  - 2868
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30030436
C2  - pmc:PMC6054684
DO  - DOI:10.1038/s41467-018-05029-3
UR  - https://inrepo02.dkfz.de/record/136814
ER  -