We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma.
- Authors
Snuderl, Matija; Kannan, Kasthuri; Pfaff, Elke; Shiyang Wang; Stafford, James M.; Serrano, Jonathan; Heguy, Adriana; Ray, Karina; Faustin, Arline; Aminova, Olga; Dolgalev, Igor; Stapleton, Stacie L.; Zagzag, David; Chiriboga, Luis; Gardner, Sharon L.; Wisoff, Jeffrey H.; Golfinos, John G.; Capper, David; Hovestadt, Volker; Rosenblum, Marc K.
- Abstract
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 genomewide 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.
- Publication
Nature Communications, 2018, Vol 9, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-05029-3