Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations
| Autor: | Sebastian Uhrig, Benedikt Brors, Charles D. Imbusch, Hanno Glimm, Peter Horak, Bogac Aybey, Malte Simon, Sadaf S. Mughal, Albrecht Stenzinger, Jonas Buchloh, Stefan Fröhling |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Leiomyosarcoma Cell Soft Tissue Neoplasms Deconvolution Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Epigenome 0302 clinical medicine Immune system medicine Humans Survival analysis Tumor-infiltrating leukocytes Proto-Oncogene Proteins c-ets Research Mesenchymal stem cell Sarcoma General Medicine Methylation Genomics medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis DNA methylation Cancer research Medicine |
| Zdroj: | Journal of Translational Medicine Journal of Translational Medicine, Vol 19, Iss 1, Pp 1-17 (2021) |
| ISSN: | 1479-5876 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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