Pituiatry tumors account for about 15% of all intracranial neoplasms. They arise from pituitary cell types due to both cell cycle trophic dysruptions leading to adenomatous growth, as well as a coupling of specific hormone gene over-expression. Thus, both tumor growth characteristics, as well as hormonal excess are the hallmarks of these invariably benign tumors. They may lead to both central compressive features due to mass expansion or invasion, as well as to specific clinical hormone hypersecretory syndromes. Although several familial syndromes have recently been characterized for specific gene mutations, the etiology of spontaneous non-familial tumorigenesis has remained largely elusive. This talk will emphasize findings for spontaneous pituitary tumorigenesis. Transgenic murine and zebrafish models will be described which recapitulate phenotypic human pituitary adenomas, and genetic mechanisms derived from these models will be translated to human clinical observations. Limited information derived directly from human tumor specimens will also be discussed, inasmuch as they relate directly to cause rather than effect of specific pituiatry adenoma subtypes. An overview of known genetic changes which underly pathogenesis of these tumors include dysrupted cell cycle proteins, including CDKs and CDK inhibitors and the RB-related cascade will be provided. Disordered genetic regulation of HMG proteins, PTTG, tumor supressor genes and cAMP-related genes will also be reviewed. Epigenetic and chromatin-associated changes leading to altered specific transcriptional patterns for cell cycle or hormone-related gene expression, may also contribute to the observed genetic changes. Given that these tumors are predominantly benign, and rarely progress to malignancy, genetic mechanisms underlying premature proliferative arrest and oncogene-induced senescence will also be reviewed. Overall, the myriad of genetic information will be integrated into a unifying hypothesis which determines the etiology of these tumors responsible for considerable patient morbidity and mortality. These insights provide direction for future subcellular approaches to therapy, and examples of such available pharmacologic agents will be presented. Thus,understanding genetic alterations in these tumors will lead to enhanced disease prognostic marker prediciton, as well as development of novel therapies.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.