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Epigenetic alterations in human parathyroid tumors

Chiara Verdelli1, Irene Forno, Valentina Vaira

  • 1Laboratory of Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy.

Endocrine
|February 28, 2015
PubMed

Insights

Epigenetic alterations like DNA methylation and microRNA changes are key in parathyroid tumor development. These changes, including histone methylation, are linked to endocrine neoplasia and primary hyperparathyroidism.

Area of Science:

  • Endocrinology
  • Oncology
  • Epigenetics

Background:

  • Parathyroid tumors are the second most common endocrine neoplasia in women.
  • They are associated with primary hyperparathyroidism, driven by PTH hypersecretion.
  • Epigenetic alterations, including DNA methylation, microRNA deregulation, and histone methylation impairment, are implicated in tumorigenesis.

Purpose of the Study:

  • To investigate the role of epigenetic modifications in parathyroid tumor development.
  • To understand the specific epigenetic changes occurring during the progression from benign to malignant parathyroid tumors.

Main Methods:

  • Analysis of DNA methylation patterns, focusing on CpG islands.
  • Assessment of microRNA expression profiles.
  • Evaluation of histone methyltransferase expression (e.g., EZH2, BMI1, RIZ1).

Main Results:

  • While global promoter hypomethylation was not observed, specific CpG island hypermethylation increased in malignant parathyroid tumors.
  • A panel of embryonic-related microRNAs was deregulated in parathyroid tumors compared to normal glands.
  • Impaired expression of histone methyltransferases (EZH2, BMI1, RIZ1) was noted, modulated by tumor suppressor genes.

Conclusions:

  • Epigenetic modifications, particularly DNA methylation and microRNA deregulation, play a significant role in parathyroid tumorigenesis.
  • An embryonic gene signature is emerging as a key factor in parathyroid tumor development.
  • Further research into the epigenetic landscape of parathyroid tumors is warranted.

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