Pituitary Tumors: Genetics and Heritable Predisposition

Pituitary tumors are the most common intracranial tumors. Most pituitary tumors are thought to be sporadic, with estimates showing that genetic heritability in the form of traditional syndromes, including multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC), accounts for only 5% of all cases. The monoclonality of pituitary tumors is a widely established model in which a genetic mutation in one cell leads to the formation of an adenoma. On a larger scale, however, the pituitary gland may contain multiple hyperplastic cells, each with its own origin. The predominant cell type within the adenoma is dependent on a variety of oncogenes and tumor suppressor genes including GSP, RAS, Cyclin D1, PTTG, and p53. Multiple other studies show germline mutations in a variety of additional genes, including AIP, BMP-4, CDKN1B, CDKN2A, CDKN2C, GADD45G, PDt-FGFR4, PKC, PRKAR1A, RB, WIF1, and ZAC. More recently, studies of genetic mutations leading to pituitary adenomas and population studies of patients and families with pituitary adenomas have revealed a significant heritable predisposition for pituitary tumors outside of traditional syndromes. These studies, while confirming the heritability of pituitary tumors, unfortunately only provide a glimpse into the multifactorial cause of pituitary adenomas.