Epigenetic-related gene expression profile in medullary thyroid cancer revealed the overexpression of the histone methyltransferases EZH2 and SMYD3 in aggressive tumours

Mol Cell Endocrinol. 2014 Jul 5;392(1-2):8-13. doi: 10.1016/j.mce.2014.04.016. Epub 2014 May 9.

Abstract

Epigenetic control of gene expression plays a major influence in the development and progression of many cancer types. Aim of the present study was to investigate the expression of epigenetic regulators in a large cohort of medullary thyroid carcinomas (MTC), correlating the data with the clinical outcome and mutational status of the patients. Taqman Low Density Arrays (TLDAs) were used to analyze expression levels of several genes involved in the epigenetic control of transcription in a series of 54 MTCs. The patients cohort included 13 familial MTCs and 41 sporadic forms; 33 hosted a RET mutation and 13 a RAS somatic mutation. The expression profiling revealed in the more aggressive diseases (i.e. occurrence of metastases; persistent disease; disease-related death) a significant increase of EZH2 and SMYD3 gene expression. The increased levels of EZH2 and SMYD3 did not correlate significantly with mutational status of RET or RAS genes. Thus, the histone methyltransferases EZH2 and SMYD3 mRNA expression may represent useful prognostic biomarkers tailoring the most appropriate follow-up and timing of therapeutic approaches.

Keywords: Epigenetics; Histone methylation; Medullary thyroid cancer; RAS; RET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Neuroendocrine
  • Child
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Invasiveness
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism
  • Thyroid Neoplasms / enzymology*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • SMYD3 protein, human

Supplementary concepts

  • Thyroid cancer, medullary