Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma

Nature Communications
Matija SnuderlMatthias A Karajannis

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.

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Citations

Jun 22, 2019·Journal of Neuropathology and Experimental Neurology·Haydee MartínezFausto J Rodriguez
Oct 28, 2019·Cold Spring Harbor Molecular Case Studies·Matija SnuderlMatthias A Karajannis
Oct 2, 2019·Frontiers in Pharmacology·Nadezhda Mironova, Valentin Vlassov
Jan 10, 2020·Expert Review of Molecular Diagnostics·Bryan K LiEric Bouffet
Dec 6, 2019·The Journal of Clinical Investigation·Barbara RiveraWilliam D Foulkes
Nov 13, 2019·Advances in Anatomic Pathology·Marissa Spino, Matija Snuderl
Apr 15, 2020·Nature Communications·Philip E D ChungEldad Zacksenhaus
Jul 18, 2020·Frontiers in Oncology·Enrico FranceschiUNKNOWN EURACAN Domain 10
Jan 10, 2020·Cancer Genetics·Andrea Cervantes-AyalcMiguel Ángel Velázquez-Flores
Dec 15, 2020·Neuro-oncology Practice·Joo Yeon NamCarlos Kamiya-Matsuoka
Feb 24, 2021·Acta Neuropathologica·Anthony P Y LiuAnnie Huang
Jun 12, 2021·Seminars in Cancer Biology·Mirjam Blattner-JohnsonElke Pfaff
May 18, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Anna Prieto-ColominaVíctor Borrell

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Datasets Mentioned

BETA
PRJNA446027

Methods Mentioned

BETA
PCR
chip
fetopsy

Key Resources (RRID) Mentioned

AB_11214420
AB_11128871

Software Mentioned

STAR
COSMIC
ToppGene
featureCounts
BWA
Annovar
Ingenuity Pathway Analysis ( IPA )
- FREEC
Nanostring
IPA ( ) Ingenuity Pathway Analysis

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