Alterazioni genetiche negli adenomi ipofisari umani.

Translated title of the contribution: Genetic changes in human pituitary adenomas

A. Spada, A. Lania

Research output: Contribution to journalArticle

Abstract

In the last few years molecular biology technologies have provided important insights into mechanisms possibly involved in pituitary tumor formation. Several evidences indicate that the majority of pituitary adenomas is monoclonal, thus implying that they derive from the replication of a single mutant cell. In about 30-40% of GH-secreting adenomas mutations at codon 201 and 227 of GNAS1 gene that codes for the Gs alpha subunit have been identified. These mutations, named gsp for Gs protein, cause the constitutive, hormone-independent, activation of adenylyl cyclase and consequent overproduction of cAMP, that is mitogenic in somatotropes. Screening studies carried out on large series of acromegalic patients carrying tumors with or without gsp oncogene failed to detect clinical differences between the two groups. The existence of mechanisms induced by gsp mutations and able to counteract the mitogenic potential of this oncogene has been hypothesized. In particular, several events including the low expression of mutant Gs, the induction of phosphodiesterases, that are involved in cAMP degradation, and of the inducible cAMP early repressor (ICER) that represses cAMP induced gene expression, together with a high sensitivity to somatostatin have been characterized in gsp positive tumors. As far as the loss of oncosuppressors is concerned, no mutations of these genes have been so far reported, while they are frequently expressed at low levels in pituitary tumors. However, the nature of initiating and promoting events involved in tumor formation remains to be clarified in the majority of pituitary tumors.

Translated title of the contributionGenetic changes in human pituitary adenomas
Original languageItalian
Pages (from-to)27-37
Number of pages11
JournalMinerva Endocrinologica
Volume28
Issue number1
Publication statusPublished - 2003

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