Over-methylation of Histone H3 Lysines Is a Common Molecular Change Among the Three Major Types of Soft-tissue Sarcoma in Patient-derived Xenograft (PDX) Mouse Models

Cancer Genomics Proteomics. 2021 Nov-Dec;18(6):715-721. doi: 10.21873/cgp.20292.

Abstract

Background/aim: Sarcomas are considered a heterogeneous disease with incomplete understanding of its molecular basis. In the present study, to further understand general molecular changes in sarcoma, patient-derived xenograft (PDX) mouse models of the three most common soft-tissue sarcomas: myxofibrosarcoma, undifferentiated pleomorphic sarcoma (UPS) and liposarcoma were established and the methylation status of histone H3 lysine marks was studied.

Materials and methods: Immunoblotting and immunohistochemical staining were used to quantify the extent of methylation of histone H3K4me3 and histone H3K9me3.

Results: In all 3 sarcoma types in PDX models, histone H3K4me3 and H3K9me3 were found highly over-methylated compared to normal muscle tissue.

Conclusion: Histone H3 lysine over-methylation may be a general basis of malignancy of the major sarcoma types.

Keywords: PDX; Sarcoma; histone H3; lysine; methionine-addiction; over-methylation.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Animals
  • Disease Models, Animal
  • Female
  • Histones / metabolism*
  • Humans
  • Male
  • Methylation
  • Mice
  • Mice, Nude
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Histones