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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Malte Simon - , Deutsches Krebsforschungszentrum (DKFZ), Universität Heidelberg (Autor:in)
  • Sadaf S. Mughal - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Peter Horak - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Sebastian Uhrig - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Jonas Buchloh - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Bogac Aybey - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Albrecht Stenzinger - , Universität Heidelberg (Autor:in)
  • Hanno Glimm - , Nationales Centrum für Tumorerkrankungen Dresden (NCT/UCC), Nationales Centrum für Tumorerkrankungen Dresden, Nationales Zentrum für Tumorerkrankungen (NCT) Dresden, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Stefan Fröhling - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Benedikt Brors - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Charles D. Imbusch - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)

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.

Details

OriginalspracheEnglisch
Aufsatznummer204
FachzeitschriftJournal of translational medicine
Jahrgang19
Ausgabenummer1
PublikationsstatusVeröffentlicht - Dez. 2021
Peer-Review-StatusJa

Externe IDs

PubMed 33980253

Schlagworte

Schlagwörter

  • Deconvolution, Sarcoma, Survival analysis, Tumor-infiltrating leukocytes