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Correction to: Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes

Authors :
Javad Nazarian
Melanie Weingart
Ping An
Brennan Harmon
Amanda Saratsis
Eric H. Raabe
Suresh N. Magge
Brian R. Rood
Tobey J. MacDonald
Sridevi Yadavilli
Roger J. Packer
Jordan Hall
Madhuri Kambhampati
Kendall Snyder
Joseph M. Devaney
Source :
Acta Neuropathologica. 140:247-247
Publication Year :
2020
Publisher :
Springer Science and Business Media LLC, 2020.

Abstract

Diffuse Intrinsic Pontine Glioma (DIPG) is a highly morbid form of pediatric brainstem glioma. Here, we present the first comprehensive protein, mRNA, and methylation profiles of fresh frozen DIPG specimens (n=14), normal brain tissue (n=10), and other pediatric brain tumors (n=17). Protein profiling identified 2,305 unique proteins indicating distinct DIPG protein expression patterns compared to other pediatric brain tumors. Western blot and immunohistochemistry validated upregulation of Clusterin (CLU), Elongation Factor 2 (EF2), and Talin-1 (TLN1) in DIPGs studied. Comparisons to mRNA expression profiles generated from tumor and adjacent normal brain tissue indicated two DIPG subgroups, characterized by upregulation of Myc (N-Myc) or Hedgehog (Hh) signaling. We validated upregulation of PTCH, a membrane receptor in the Hh signaling pathway, in a subgroup of DIPG specimens. DNA methylation analysis indicated global hypomethylation of DIPG compared to adjacent normal tissue specimens, with differential methylation of 24 genes involved in Hh and Myc pathways, correlating with protein and mRNA expression patterns. Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77% of our DIPG cohort. Supervised analysis revealed a unique methylation pattern in mutated specimens compared to the wild type DIPG samples.

Details

ISSN :
14320533 and 00016322
Volume :
140
Database :
OpenAIRE
Journal :
Acta Neuropathologica
Accession number :
edsair.doi.dedup.....c2d242033a476a98f2a2fe2a9d1134bd