Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma Journal Article


Authors: Snuderl, M.; Kannan, K.; Pfaff, E.; Wang, S.; Stafford, J. M.; Serrano, J.; Heguy, A.; Ray, K.; Faustin, A.; Aminova, O.; Dolgalev, I.; Stapleton, S. L.; Zagzag, D.; Chiriboga, L.; Gardner, S. L.; Wisoff, J. H.; Golfinos, J. G.; Capper, D.; Hovestadt, V.; Rosenblum, M. K.; Placantonakis, D. G.; LeBoeuf, S. E.; Papagiannakopoulos, T. Y.; Chavez, L.; Ahsan, S.; Eberhart, C. G.; Pfister, S. M.; Jones, D. T. W.; Karajannis, M. A.
Article Title: Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma
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 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. © 2018, The Author(s).
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-07-20
Start Page: 2868
Language: English
DOI: 10.1038/s41467-018-05029-3
PROVIDER: scopus
PMCID: PMC6054684
PUBMED: 30030436
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Marc Rosenblum
    249 Rosenblum
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