Next Article in Journal
Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis
Previous Article in Journal
Multiplexed Immunohistochemistry for Molecular and Immune Profiling in Lung Cancer—Just About Ready for Prime-Time?
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Cancers 2019, 11(3), 284; https://doi.org/10.3390/cancers11030284

Gliosarcoma Is Driven by Alterations in PI3K/Akt, RAS/MAPK Pathways and Characterized by Collagen Gene Expression Signature

1
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland
2
Laboratory of Bioinformatics, Nencki Institute of Experimental Biology, Warsaw 02-093, Poland
3
Department of Neurosurgery, Institute of Psychiatry and Neurology, Warsaw 02-957, Poland
4
Department of Pathology, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
5
Neurosurgical Research, University Clinics, 80539 LMU Munich, Germany
6
Institute of Neuropathology, University Medical Center, 20251 Hamburg-Eppendorf, Germany
7
Research Institute Children’s Cancer Center Hamburg, 20251 Hamburg, Germany
8
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
9
Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Received: 4 February 2019 / Revised: 18 February 2019 / Accepted: 19 February 2019 / Published: 27 February 2019
Full-Text   |   PDF [23696 KB, uploaded 1 March 2019]   |  
  |   Review Reports

Abstract

Gliosarcoma is a very rare brain tumor reported to be a variant of glioblastoma (GBM), IDH-wildtype. While differences in molecular and histological features between gliosarcoma and GBM were reported, detailed information on the genetic background of this tumor is lacking. We intend to fill in this knowledge gap by the complex analysis of somatic mutations, indels, copy number variations, translocations and gene expression patterns in gliosarcomas. Using next generation sequencing, we determined somatic mutations, copy number variations (CNVs) and translocations in 10 gliosarcomas. Six tumors have been further subjected to RNA sequencing analysis and gene expression patterns have been compared to those of GBMs. We demonstrate that gliosarcoma bears somatic alterations in gene coding for PI3K/Akt (PTEN, PI3K) and RAS/MAPK (NF1, BRAF) signaling pathways that are crucial for tumor growth. Interestingly, the frequency of PTEN alterations in gliosarcomas was much higher than in GBMs. Aberrations of PTEN were the most frequent and occurred in 70% of samples. We identified genes differentially expressed in gliosarcoma compared to GBM (including collagen signature) and confirmed a difference in the protein level by immunohistochemistry. We found several novel translocations (including translocations in the RABGEF1 gene) creating potentially unfavorable combinations. Collected results on genetic alterations and transcriptomic profiles offer new insights into gliosarcoma pathobiology, highlight differences in gliosarcoma and GBM genetic backgrounds and point out to distinct molecular cues for targeted treatment. View Full-Text
Keywords: gliosarcoma; glioblastoma; transcriptome; PI3K/Akt; RAS/MAPK; mutation; collagen gliosarcoma; glioblastoma; transcriptome; PI3K/Akt; RAS/MAPK; mutation; collagen
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Wojtas, B.; Gielniewski, B.; Wojnicki, K.; Maleszewska, M.; Mondal, S.S.; Nauman, P.; Grajkowska, W.; Glass, R.; Schüller, U.; Herold-Mende, C.; Kaminska, B. Gliosarcoma Is Driven by Alterations in PI3K/Akt, RAS/MAPK Pathways and Characterized by Collagen Gene Expression Signature. Cancers 2019, 11, 284.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top