Table 1.
The list of disease-related genes that are involved in the pathogenesis of somatotroph tumors. ND: not determined.
| Germline or Mosaic Mutations | Reported Incidence of Mutations | Concomitant Development of the Tumors | The Mechanisms of Tumorigenesis by the Gene Mutation |
|---|---|---|---|
| MENIN (MEN1) | 1/30,000~1/40,000 | parathyroid adenoma, pancreatic neuroendocrine tumor | Influence on cell proliferation, cell signaling, transcriptional regulation, and genome stability |
| Cyclin Dependent Kinase Inhibitor 1B (CDKN1B) | up to 3% of cases with negative MEN1 mutation | corticotroph adenoma, parathyroid adenoma | Dysregulation of the cell cycle. |
| Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha (PRKAR1A) | 750 cases | skin lesions, cutaneous and heart myxomas, PPNAD, large cell calcifying Sertoli cell tumor/ calcification of testis, thyroid carcinoma or multiple hypoechoic nodules, breast ductal adenoma psammomatous melanotic schwannomas, blue nevus, osteochondromyxoma | Inactivating mutations of PRKAR1A lead to uncontrolled activation of cAMP-dependent kinase activity in affected tissues |
| GNAS Complex Locus (GNAS1) | 1/100,000~1/1,000,000 live births | fibrous dysplasia, precocious puberty, café-au-lait skin lesions | A constitutively activated cAMP pathway leading to persistent GH hypersecretion and cell proliferation. |
| Aryl Hydrocarbon Receptor-Interacting Protein (AIP) | 10% of FIPA | none | Elevated concentrations of cAMP |
| G Protein-Coupled Receptor 101 (GPR101) | 7.8–10% of gigantism patients | none | Activation of an orphan G protein-coupled receptor and increased cAMP levels, which is a key factor in GH secretion and cell proliferation in response to GHRH |
| Succinate dehydrogenase (SDHx) | very rare | pheochromocytoma/paraganglioma (PPGL) | The accumulation of onco-metabolites that inhibit degradation of hypoxia transcription factor (HIFα) |
| MYC associated factor X (MAX) | very rare | pheochromocytoma/paraganglioma (PPGL), neuroendocrine cells, renal tumors, small cell lung cancer | To interact with other parts of the MAX-MLX network, which is responsible for the integration of cellular signals and modulates the expression of another gene |
| Neurofibromatosis type 1 (NF1) | 1:2500–1:3500 live births. | optic pathway gliomas, cutaneous neurofibromas, cafe-au-lait skin lesions, intertriginous freckling, Lisch nodules, brain tumors | Involved in cell growth and proliferation, by inhibiting RAS activity and regulation of cAMP levels |
| Tuberous sclerosis complex (TSC) | very rare | multiple hamartomas in brain, lungs, heart, skin, and kidney | ND |