The role of genetic and epigenetic changes in pituitary tumorigenesis

Neurol Med Chir (Tokyo). 2014;54(12):943-57. doi: 10.2176/nmc.ra.2014-0184. Epub 2014 Nov 29.

Abstract

Pituitary adenomas are one of the most common intracranial tumors. Despite their benign nature, dysregulation of hormone secretion causes systemic metabolic deterioration, resulting in high mortality and an impaired quality of life. Tumorigenic pathogenesis of pituitary adenomas is mainly investigated by performing genetic analyses of somatic mutations in the tumor or germline mutations in patients. Genetically modified mouse models, which develop pituitary adenomas, are also used. Genetic analysis in rare familial pituitary adenomas, including multiple endocrine neoplasia type 1 and type 4, Carney complex, familial isolated pituitary adenomas, and succinate dehydrogenases (SDHs)-mediated paraganglioma syndrome, revealed several causal germline mutations and sporadic somatic mutations in these genes. The analysis of genetically modified mouse models exhibiting pituitary adenomas has revealed the underlying mechanisms, where cell cycle regulatory molecules, tumor suppressors, and growth factor signaling are involved in pituitary tumorigenesis. Furthermore, accumulating evidence suggests that epigenetic changes, including deoxyribonucleic acid (DNA) methylation, histone modification, micro ribonucleic acids (RNAs), and long noncoding RNAs play a pivotal role. The elucidation of precise mechanisms of pituitary tumorigenesis can contribute to the development of novel targeted therapy for pituitary adenomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoma / genetics*
  • Adenoma / therapy
  • Cell Transformation, Neoplastic / genetics*
  • DNA Methylation / genetics
  • Epigenesis, Genetic / genetics*
  • Germ-Line Mutation / genetics
  • Histone Code / genetics
  • Humans
  • MicroRNAs / genetics
  • Molecular Targeted Therapy
  • Pituitary Neoplasms / genetics*
  • Pituitary Neoplasms / therapy

Substances

  • MicroRNAs