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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Soft Tissue Sarcoma | Research

Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations

Authors: Malte Simon, Sadaf S. Mughal, Peter Horak, Sebastian Uhrig, Jonas Buchloh, Bogac Aybey, Albrecht Stenzinger, Hanno Glimm, Stefan Fröhling, Benedikt Brors, Charles D. Imbusch

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal tumors for which response to immunotherapies is not well established. Therefore, it is important to risk-stratify and identify STS patients who will most likely benefit from these treatments.

Results

To reveal shared and distinct methylation signatures present in STS, we performed unsupervised deconvolution of DNA methylation data from the TCGA sarcoma and an independent validation cohort. We showed that leiomyosarcoma can be subclassified into three distinct methylation groups. More importantly, we identified a component associated with tumor-infiltrating leukocytes, which suggests varying degrees of immune cell infiltration in STS subtypes and an association with prognosis. We further investigated the genomic alterations that may influence tumor infiltration by leukocytes including RB1 loss in undifferentiated pleomorphic sarcomas and ELK3 amplification in dedifferentiated liposarcomas.

Conclusions

In summary, we have leveraged unsupervised methylation-based deconvolution to characterize the immune compartment and molecularly stratify subtypes in STS, which may benefit precision medicine in the future.
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Metadata
Title
Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations
Authors
Malte Simon
Sadaf S. Mughal
Peter Horak
Sebastian Uhrig
Jonas Buchloh
Bogac Aybey
Albrecht Stenzinger
Hanno Glimm
Stefan Fröhling
Benedikt Brors
Charles D. Imbusch
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-02858-7

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