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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Malte Simon - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Sadaf S. Mughal - , German Cancer Research Center (DKFZ) (Author)
  • Peter Horak - , German Cancer Research Center (DKFZ) (Author)
  • Sebastian Uhrig - , German Cancer Research Center (DKFZ) (Author)
  • Jonas Buchloh - , German Cancer Research Center (DKFZ) (Author)
  • Bogac Aybey - , German Cancer Research Center (DKFZ) (Author)
  • Albrecht Stenzinger - , Heidelberg University  (Author)
  • Hanno Glimm - , National Center for Tumor Diseases Dresden (NCT/UCC), National Center for Tumor Diseases Dresden, National Center for Tumor Diseases (NCT) Dresden, University Hospital Carl Gustav Carus Dresden (Author)
  • Stefan Fröhling - , German Cancer Research Center (DKFZ) (Author)
  • Benedikt Brors - , German Cancer Research Center (DKFZ) (Author)
  • Charles D. Imbusch - , German Cancer Research Center (DKFZ) (Author)

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

Original languageEnglish
Article number204
JournalJournal of translational medicine
Volume19
Issue number1
Publication statusPublished - Dec 2021
Peer-reviewedYes

External IDs

PubMed 33980253

Keywords

Keywords

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