Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma

Matija Snuderl, Kasthuri Kannan, Elke Pfaff, Shiyang Wang, James M. Stafford, Jonathan Serrano, Adriana Heguy, Karina Ray, Arline Faustin, Olga Aminova, Igor Dolgalev, Stacie L. Stapleton, David Zagzag, Luis Chiriboga, Sharon L. Gardner, Jeffrey H. Wisoff, John G. Golfinos, David Capper, Volker Hovestadt, Marc K. Rosenblum, Dimitris G. Placantonakis, Sarah E. LeBoeuf, Thales Y. Papagiannakopoulos, Lukas Chavez, Sama Ahsan, Charles G. Eberhart, Stefan M. Pfister, David T. W. Jones and Matthias A. Karajannis ()
Additional contact information
Matija Snuderl: NYU Langone Health
Kasthuri Kannan: NYU Langone Health
Elke Pfaff: Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
Shiyang Wang: Division of Pediatric Hematology/Oncology, NYU Langone Health
James M. Stafford: Department of Biochemistry and Molecular Pharmacology, NYU Langone Health
Jonathan Serrano: Genome Technology Center, NYU Langone Health
Adriana Heguy: NYU Langone Health
Karina Ray: Genome Technology Center, NYU Langone Health
Arline Faustin: NYU Langone Health
Olga Aminova: Genome Technology Center, NYU Langone Health
Igor Dolgalev: NYU Langone Health
Stacie L. Stapleton: Cancer and Blood Disorders Institute
David Zagzag: NYU Langone Health
Luis Chiriboga: NYU Langone Health
Sharon L. Gardner: NYU Langone Health
Jeffrey H. Wisoff: Department of Neurosurgery, NYU Langone Health
John G. Golfinos: Department of Neurosurgery, NYU Langone Health
David Capper: University of Heidelberg
Volker Hovestadt: German Cancer Research Center (DKFZ)
Marc K. Rosenblum: Memorial Sloan Kettering Cancer Center
Dimitris G. Placantonakis: Cancer and Blood Disorders Institute
Sarah E. LeBoeuf: NYU Langone Health
Thales Y. Papagiannakopoulos: NYU Langone Health
Lukas Chavez: German Cancer Research Center (DKFZ)
Sama Ahsan: Johns Hopkins Hospital
Charles G. Eberhart: Johns Hopkins Hospital
Stefan M. Pfister: Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
David T. W. Jones: Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
Matthias A. Karajannis: Memorial Sloan Kettering Cancer Center

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05029-3

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