학술논문
Epigenetic age acceleration is a distinctive trait of epithelioid sarcoma with potential therapeutic implications.
Document Type
Academic Journal
Author
Haefliger S; Research Department of Pathology, University College London, UCL Cancer Institute, London, UK.; Bone Tumor Reference Centre, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.; Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, London, UK.; Chervova O; Medical Genomics Research Group, University College London, UCL Cancer Institute, London, UK.; Davies C; Research Department of Pathology, University College London, UCL Cancer Institute, London, UK.; Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, London, UK.; Loh C; Altos Labs, Cambridge Institute of Science, Cambridge, UK.; Tirabosco R; Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, London, UK.; Amary F; Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, London, UK.; Pillay N; Research Department of Pathology, University College London, UCL Cancer Institute, London, UK.; Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, London, UK.; Horvath S; Altos Labs, Cambridge Institute of Science, Cambridge, UK.; Beck S; Medical Genomics Research Group, University College London, UCL Cancer Institute, London, UK.; Flanagan AM; Research Department of Pathology, University College London, UCL Cancer Institute, London, UK. a.flanagan@ucl.ac.uk.; Department of Histopathology, Royal National Orthopaedic Hospital, Stanmore, London, UK. a.flanagan@ucl.ac.uk.; Lyskjær I; Research Department of Pathology, University College London, UCL Cancer Institute, London, UK.; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Source
Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101686284 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2509-2723 (Electronic) Linking ISSN: 25092723 NLM ISO Abbreviation: Geroscience Subsets: MEDLINE
Subject
Language
English
Abstract
Recently, DNA methylation clocks have been proven to be precise age predictors, and the application of these clocks in cancer tissue has revealed a global age acceleration in a majority of cancer subtypes when compared to normal tissue from the same individual. The polycomb repressor complex 2 plays a pivotal role in the aging process, and its targets have been shown to be enriched in CpG sites that gain methylation with age. This complex is further regulated by the chromatin remodeling complex SWItch/Sucrose Non-Fermentable and its core subunit, notably the tumor suppressor gene SMARCB1, which under physiological conditions inhibits the activity of the polycomb repressor complex 2. Hence, the loss of function of core members of the SWItch/sucrose non-fermentable complex, such as the tumor suppressor gene SMARCB1, results in increased activity of polycomb repressor complex 2 and interferes with the aging process. SMARCB1-deficient neoplasms represent a family of rare tumors, including amongst others malignant rhabdoid tumors, atypical teratoid and rhabdoid tumors, and epithelioid sarcomas. As aging pathways have recently been proposed as therapeutic targets for various cancer types, these tumors represent candidates for testing such treatments. Here, by deriving epigenetic age scores from more than 1000 tumor samples, we identified epigenetic age acceleration as a hallmark feature of epithelioid sarcoma. This observation highlights the potential of targeting aging pathways as an innovative treatment approach for patients with epithelioid sarcoma.
(© 2024. The Author(s).)
(© 2024. The Author(s).)