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

Cancers
Bartosz WojtasBozena Kaminska

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...Continue Reading

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Citations

Jun 12, 2019·Cancers·Felix Behling, Jens Schittenhelm
Oct 14, 2020·Archives of Biochemistry and Biophysics·Hongzao NiJing Li
May 20, 2021·Radiology Case Reports·Renato Masson de Almeida PradoGustavo Dalul Gomez
Jun 25, 2021·BMC Neurology·Christopher DardisSurasak Phuphanich
Oct 5, 2021·CNS Neuroscience & Therapeutics·Jie LiZhi-Qiang Li
Nov 26, 2020·Journal of Pediatric Hematology/oncology·Richard T GrahamArnab Chakravarti
Dec 31, 2021·Acta Neuropathologica·Abigail K SuwalaDavid E Reuss

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Methods Mentioned

BETA
RNAseq
RNA-seq
nucleotide exchange
PCR
exome sequencing
Profiler

Software Mentioned

GenVisR
absCNseq
SeqCap EZ Choice Library
TopHat
Varscan2 Effect Predictor ( VEP
SeqCap EZ
BWA aligner
R
Ensembl
Tophat2

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