A mutation and expression analysis of the oncogene BRAF in pituitary adenomas

Iain Ewing1, Stephen Pedder-Smith, Giulia Franchi

  • 1Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, UK.

Clinical Endocrinology
|February 17, 2007
PubMed
Abstract

Insights

BRAF V600E mutations are not found in pituitary adenomas. However, B-Raf mRNA and protein overexpression is observed in nonfunctioning pituitary adenomas (NFPAs), suggesting Ras-B-Raf-MAP kinase pathway overactivity.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • BRAF is a key oncogene in melanoma and thyroid cancer, often mutated at V600E, activating the Ras-mitogen-activated protein kinase (MAPK) pathway.
  • The role of BRAF mutations or overexpression in pituitary adenomas is not well understood.

Purpose of the Study:

  • To investigate the presence of BRAF V600E mutations in pituitary adenomas.
  • To assess B-Raf mRNA and protein expression levels in pituitary adenomas compared to normal pituitary tissue.

Main Methods:

  • Sequencing of 37 pituitary adenomas for BRAF V600E mutation.
  • Semi-quantitative and real-time quantitative PCR to measure B-Raf mRNA expression in normal pituitaries and various pituitary adenomas, including nonfunctioning pituitary adenomas (NFPAs).
  • Western blot analysis to evaluate B-Raf protein expression in normal pituitaries and NFPAs.

Main Results:

  • No BRAF V600E mutations were detected in any of the pituitary adenomas analyzed.
  • B-Raf mRNA was significantly overexpressed in pituitary adenomas, particularly in NFPAs, compared to normal pituitary tissue.
  • B-Raf protein expression in NFPAs was variable but correlated with higher B-Raf mRNA levels.

Conclusions:

  • BRAF V600E mutations are infrequent in pituitary adenomas.
  • Overexpression of B-Raf mRNA and protein is a potential characteristic of NFPAs.
  • These findings suggest the Ras-B-Raf-MAP kinase pathway is overactive in NFPAs.

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