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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
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The epigenomics of sarcoma.

Benjamin A Nacev1,2, Kevin B Jones3,4, Andrew M Intlekofer5

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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|August 13, 2020
PubMed
Summary

Chromatin regulators are altered in sarcomas, driving disease biology. Understanding these epigenetic changes offers new therapeutic strategies for these rare cancers.

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Area of Science:

  • Molecular Biology
  • Oncology
  • Epigenetics

Background:

  • Epigenetic regulation, including DNA methylation and histone modification, controls fundamental cellular processes.
  • Alterations in chromatin regulators are prevalent in mesenchymal neoplasms, particularly sarcomas.
  • Sarcomas exhibit diverse genetic, biological, and clinical features.

Purpose of the Study:

  • To review sarcomas driven by alterations in chromatin pathways.
  • To emphasize dysregulation of epigenetic control levels in sarcoma development.
  • To discuss current and future therapeutic strategies targeting chromatin dysregulation.

Main Methods:

  • Review of scientific literature focusing on epigenetic mechanisms in sarcomas.
  • Emphasis on alterations in metabolic enzymes, histone genes, chromatin remodelling complexes, and chromatin structure.
  • Analysis of specific sarcoma types including chondroblastoma, giant cell tumour of bone, chondrosarcoma, malignant peripheral nerve sheath tumour, synovial sarcoma, epithelioid sarcoma, and Ewing sarcoma.

Main Results:

  • Dysregulation of DNA methylation, histone modifications, nucleosome remodelling, and 3D chromatin structure drives sarcoma biology.
  • Specific mechanisms include altered metabolic enzymes, histone gene mutations, loss/fusions in chromatin complexes, and disrupted higher-order chromatin structure.
  • Epigenetic tumorigenesis is implicated in various bone and soft tissue sarcomas, often affecting younger patients.

Conclusions:

  • Chromatin pathway alterations are key drivers in a significant subset of sarcomas.
  • Understanding these epigenetic dysregulations provides a basis for novel therapeutic interventions.
  • Targeting epigenetic mechanisms represents a promising avenue for future sarcoma treatment development.