Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma

Nat Commun. 2018 Jul 20;9(1):2868. doi: 10.1038/s41467-018-05029-3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Child
  • Cytoskeletal Proteins
  • DEAD-box RNA Helicases / genetics
  • DNA Methylation
  • Exome
  • Gene Deletion*
  • Gene Duplication*
  • Genome, Human
  • Homozygote
  • Humans
  • Middle Aged
  • Muscle Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Pineal Gland / pathology
  • Pinealoma / genetics*
  • Protein Domains
  • Ribonuclease III / genetics*
  • Transcriptome


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Muscle Proteins
  • Nuclear Proteins
  • PDE4DIP protein, human
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases