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An extracellular vesicle-related gene expression signature identifies high-risk patients in medulloblastoma

Medulloblastoma (MB) is a malignant brain tumor in childhood. It comprises 4 subgroups with different clinical behaviors. The aim of this study was to characterize the transcriptomic landscape of MB, both at the level of individual tumors as well as in large patient cohorts.We used a combination of...

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Main Authors: Albert, Thomas (Author) , Interlandi, Marta (Author) , Sill, Martin (Author) , Graf, Monika (Author) , Moreno, Natalia (Author) , Menck, Kerstin (Author) , Rohlmann, Astrid (Author) , Melcher, Viktoria (Author) , Korbanka, Sonja (Author) , Meyer zu Hörste, Gerd (Author) , Lautwein, Tobias (Author) , Frühwald, Michael C (Author) , Krebs, Christian F (Author) , Holdhof, Dörthe (Author) , Schoof, Melanie (Author) , Bleckmann, Annalen (Author) , Missler, Markus (Author) , Dugas, Martin (Author) , Schüller, Ulrich (Author) , Jäger, Natalie (Author) , Pfister, Stefan (Author) , Kerl, Kornelius (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Neuro-Oncology
Year: 2021, Volume: 23, Issue: 4, Pages: 586-598
ISSN:1523-5866
DOI:10.1093/neuonc/noaa254
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/noaa254
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/neuro-oncology/article/23/4/586/5974128
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Author Notes:Thomas K. Albert, Marta Interlandi, Martin Sill, Monika Graf, Natalia Moreno, Kerstin Menck, Astrid Rohlmann, Viktoria Melcher, Sonja Korbanka, Gerd Meyer zu Hörste, Tobias Lautwein, Michael C. Frühwald, Christian F. Krebs, Dörthe Holdhof, Melanie Schoof, Annalen Bleckmann, Markus Missler, Martin Dugas, Ulrich Schüller, Natalie Jäger, Stefan M. Pfister, and Kornelius Kerl
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Summary:Medulloblastoma (MB) is a malignant brain tumor in childhood. It comprises 4 subgroups with different clinical behaviors. The aim of this study was to characterize the transcriptomic landscape of MB, both at the level of individual tumors as well as in large patient cohorts.We used a combination of single-cell transcriptomics, cell culture models and biophysical methods such as nanoparticle tracking analysis and electron microscopy to investigate intercellular communication in the MB tumor niche.Tumor cells of the sonic hedgehog (SHH)-MB subgroup show a differentiation blockade. These cells undergo extensive metabolic reprogramming. The gene expression profiles of individual tumor cells show a partial convergence with those of tumor-associated glial and immune cells. One possible cause is the transfer of extracellular vesicles (EVs) between cells in the tumor niche. We were able to detect EVs in co-culture models of MB tumor cells and oligodendrocytes. We also identified a gene expression signature, EVS, which shows overlap with the proteome profile of large oncosomes from prostate cancer cells. This signature is also present in MB patient samples. A high EVS expression is one common characteristic of tumors that occur in high-risk patients from different MB subgroups or subtypes.With EVS, our study uncovered a novel gene expression signature that has a high prognostic significance across MB subgroups.
Item Description:Advance access date 11 November 2020
Gesehen am 09.07.2021
Physical Description:Online Resource
ISSN:1523-5866
DOI:10.1093/neuonc/noaa254

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