Genetics of pituitary tumors

Focus on G-protein mutations

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

In recent years the demonstration that human pituitary adenomas are monoclonal in origin has provided further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. While common oncogenes, such as Ras, are only exceptionally involved, the only mutations identified in a significant proportion of pituitary tumors, and particular in GH-secreting adenomas, occur in the Gsα gene (GNAS1) and cause constitutive activation of the cAMP pathway (gsp oncogene). Moreover, pituitary tumors overexpress hypothalamic releasing hormones, growth factors, and their receptors as well as cyclins involved in cell cycle progression. As far as the role of tumor suppressor genes in pituitary tumorigenesis is concerned, reduced expression of these genes seems to frequently occur in pituitary tumors as a consequence of abnormal methylation processes. Although the only mutational change so far identified in pituitary tumors is the gsp oncogene, this oncogene is not associated with a clear phenotype in patients bearing positive tumors. Mechanisms able to counteract the cAMP pathway, such as high sensitivity to somatostatin, and induction of genes with opposite actions, such as phosphodiesterases, CREB end ICER, or instability of mutant Gsα, have been proposed to account for the lack of genotype/phenotype relationships.

Original languageEnglish
Pages (from-to)1004-1017
Number of pages14
JournalExperimental Biology and Medicine
Volume228
Issue number9
Publication statusPublished - Oct 2003

Fingerprint

Pituitary Neoplasms
GTP-Binding Proteins
Tumors
Oncogenes
Mutation
Genes
Tumor Suppressor Genes
Pituitary Hormone-Releasing Hormones
Phenotype
Cyclins
Growth Factor Receptors
Proto-Oncogenes
Bearings (structural)
Phosphoric Diester Hydrolases
Chemical activation
Somatostatin
Adenoma
Methylation
Neoplasms
Cell Cycle

Keywords

  • cAMP
  • gsp
  • Oncogene
  • Pituitary adenomas
  • Tumor suppressor genes genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Genetics of pituitary tumors : Focus on G-protein mutations. / Lania, Andrea; Mantovani, Giovanna; Spada, Anna.

In: Experimental Biology and Medicine, Vol. 228, No. 9, 10.2003, p. 1004-1017.

Research output: Contribution to journalArticle

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