Genetics of Pituitary Adenoma

Abstract

Abstract Genetic changes of pituitary have been investigated during several decades and have been identified as germ line mutations, including MEN1 , PRKAR1A , AIP , CDKN1B and SDHx genes, and somatic mutations including GNAS and PIK3CA genes. In addition to these genetic changes, further novel genes were recently identified related to childhood pituitary tumours including DICER1 and GPR101 . And somatic USP8 gene mutations were found in 35–62% of Cushing disease by next‐generation sequencing technique. Furthermore, Genome‐wide association study of pituitary adenomas and whole‐genome sequencing of GH ‐secreting adenomas were reported. From the studies of genetically engineered animals which develop pituitary adenomas, predominant genes related to cell cycle ( Rb , p27 , p18 , PTTG1 , HMGAs , MEN1 and Cdk4 ) and cAMP signalling ( Prkar1a , D2r , Ghrhr and Aip ) have been identified. Key Concepts Genetic changes in human pituitary adenomas are identified predominantly from germ line mutations of hereditary syndromes. Some genes related to germ line mutations were also identified in somatic mutations. Recent developments of somatic mutations using next‐generation sequencing are updated. Genetically engineered animal models of pituitary adenomas are summarised. Further epigenetic and proteomic analyses are important in pituitary adenomas.