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Changes in DNA 5-Hydroxymethylcytosine Levels and the Underlying Mechanism in Non-functioning Pituitary Adenomas

Yiwen Xu1, Yamei Niu2, Kan Deng3

  • 1Department of Pediatrics, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.

Frontiers in Endocrinology
|August 11, 2020
PubMed

Insights

This study reveals significantly lower genomic 5-hydroxymethylcytosine (5hmC) levels in non-functioning pituitary adenomas (NFPAs). These findings suggest a role for ten-eleven translocation 2 (TET2) in NFPA pathogenesis.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Oncology

Background:

  • Pituitary adenomas are common tumors, with non-functioning pituitary adenomas (NFPAs) representing a significant subset.
  • Epigenetic alterations, including DNA modifications, are increasingly recognized as drivers of tumorigenesis.
  • 5-hydroxymethylcytosine (5hmC), a key epigenetic mark involved in DNA demethylation, is regulated by ten-eleven translocation (TET) enzymes.

Purpose of the Study:

  • To investigate the role of genomic 5-hydroxymethylcytosine (5hmC) levels and ten-eleven translocation 2 (TET2) in the pathogenesis of non-functioning pituitary adenomas (NFPAs).
  • To compare 5hmC levels and TET2 expression in NFPAs versus normal pituitary tissues.
  • To explore the relationship between 5hmC levels, TET2 expression, localization, and genetic alterations in NFPAs.

Main Methods:

  • Quantification of genomic 5-hydroxymethylcytosine (5hmC) levels in 57 NFPAs and 5 normal pituitary glands using established methodologies.
  • Assessment of ten-eleven translocation 2 (TET2) expression, distribution, and genetic alterations within the NFPA samples.
  • Statistical analysis to determine correlations between 5hmC levels, TET2 parameters, and clinical data.

Main Results:

  • Genomic 5hmC levels were significantly lower in NFPAs compared to normal pituitary glands (P < 0.0001).
  • A positive correlation was observed between 5hmC levels and both total and nuclear TET2 expression in NFPAs (P = 0.018 and P = 0.019, respectively).
  • NFPAs with TET2 mutations (p.P29R) exhibited significantly lower genomic 5hmC levels than wild-type NFPAs (P = 0.021).

Conclusions:

  • This study provides the first evidence of genomic 5-hydroxymethylcytosine (5hmC) loss in human non-functioning pituitary adenomas (NFPAs).
  • Reduced 5hmC levels in NFPAs are associated with altered ten-eleven translocation 2 (TET2) expression, subcellular localization, and genetic mutations.
  • These findings highlight the potential involvement of TET2-mediated epigenetic dysregulation in the development of NFPAs.
Keywords:
5hmCDNA demethylationNFPAsTET2ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)

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