DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia

Ceska Gynekol. 2024;89(4):261-268. doi: 10.48095/cccg2024261.

Abstract

Objective: To investigate DNA methylation of specific tumor suppressor genes in endometrial hyperplasia compared to normal endometrial tissue. File and methodology: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 40 tissue samples with atypical endometrial hyperplasia, 40 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with a normal endometrium.

Results and conclusion: Differences in DNA methylation among the groups were found in TWIST1, GATA4, MUS81, and NTRK1 genes (TWIST1: atypical hyperplasia 67.5%, benign hyperplasia 2.5%, normal endometrium 22.5%; P < 0.00001; GATA4: atypical hyperplasia 95%, benign hyperplasia 65%, normal endometrium 22.5%; P < 0.00001; MUS81: atypical hyperplasia 57.5%, benign hyperplasia 22.5%, normal endometrium 5%; P < 0.00001; NTRK1: atypical hyperplasia 65%, benign hyperplasia 27.5%, normal endometrium 10%; P < 0.00001). Higher methylation rates were observed for the tumor suppressor genes of TWIST1, GATA4, MUS81, and NTRK1 in samples with atypical endometrial hyperplasia compared to samples with normal endometrial tissue, and higher methylation rates were found in samples with atypical endometrial hyperplasia compared to samples of benign endometrial hyperplasia. DNA methylation of TWIST1, GATA4, MUS81, and NTRK1 is involved in the pathogenesis of atypical endometrial hyperplasia.

Keywords: Epigenetics; GATA4; MUS81; Methylation; NTRK1; TWIST1; curettage; endometrial hyperplasia.

MeSH terms

  • Adult
  • DNA Methylation*
  • DNA-Binding Proteins / genetics
  • Endometrial Hyperplasia* / genetics
  • Endometrial Hyperplasia* / metabolism
  • Endometrial Hyperplasia* / pathology
  • Endonucleases / genetics
  • Female
  • GATA4 Transcription Factor* / genetics
  • GATA4 Transcription Factor* / metabolism
  • Genes, Tumor Suppressor
  • Humans
  • Middle Aged
  • Nuclear Proteins / genetics
  • Receptor, trkA* / genetics
  • Twist-Related Protein 1* / genetics

Substances

  • GATA4 protein, human
  • GATA4 Transcription Factor
  • NTRK1 protein, human
  • Nuclear Proteins
  • Receptor, trkA
  • Twist-Related Protein 1
  • TWIST1 protein, human
  • MUS81 protein, human
  • DNA-Binding Proteins
  • Endonucleases