Genetic aspects of pituitary tumors.

Pituitary adenomas arise from the replication of a single mutated cell in which growth advantage may result from either activation of protooncogenes or inactivation of antioncogenes. The search for oncogenes in the genesis of these tumors has yielded negative results except for the gsp oncogene, that has been identified in about 30-40% of GH-secreting adenomas. gsp mutations cause constitutive activation of the Gs alpha subunit, leading to elevated cAMP formation and growth hormone hypersecretion. In the remaining tumor types several lines of evidence suggest that genes implicated in cell proliferation, such as early immediate genes, growth factors and growth factor receptors, are overexpressed. As far as the loss of antioncogenes in pituitary adenomas is concerned, no inactivating mutations of these genes have yet been identified in pituitary adenomas. However, despite the lack of mutations, several antioncogene proteins have been detected at extremely low levels in pituitary adenomas, consistent with a possible role of these tumor suppressors in pituitary tumor formation.