Pituitary Adenoma Predisposition Caused by Germline Mutations in the AIP Gene

• Published in: Science (American Association for the Advancement of Science) Vol. 312; no. 5777; pp. 1228 - 1230
• Main Authors: Vierimaa, Outi, Georgitsi, Marianthi, Lehtonen, Rainer, Vahteristo, Pia, Kokko, Antti, Raitila, Anniina, Tuppurainen, Karoliina, Ebeling, Tapani M.L, Salmela, Pasi I, Paschke, Ralf, Gündogdu, Sadi, De Menis, Ernesto, Mäkinen, Markus J, Launonen, Virpi, Karhu, Auli, Aaltonen, Lauri A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 26.05.2006; The American Association for the Advancement of Science
• Subjects: Acromegaly; Adenoma - genetics; Age of Onset; Biological and medical sciences; Birth control; Cohort Studies; Diabetes; Exons; Female; Finland; Gene Expression Profiling; Genes; Genetic mutation; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; Germline mutation; Gigantism; Growth Hormone-Secreting Pituitary Adenoma - genetics; Gynecology. Andrology. Obstetrics; Haplotypes; Heterozygote; Hormonal contraception; Humans; Intracellular Signaling Peptides and Proteins; Lod Score; Loss of Heterozygosity; Male; Medical genetics; Medical sciences; Multiple endocrine neoplasia type 1; Mutation; Oligonucleotide Array Sequence Analysis; Pedigree; Penetrance; Pituitary gland; Pituitary neoplasms; Pituitary Neoplasms - genetics; Polymorphism, Single Nucleotide; Prolactinoma - genetics; Proteins - genetics; Proteins - physiology; Sex Distribution; Tumors; Finland; Endocrinopathy; Human; Gene; Germ line; Pituitary diseases; Predisposition; Genetics; Benign neoplasm; Mutation; Pituitary Adenoma
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1126100

Pituitary adenomas are common in the general population, and understanding their molecular basis is of great interest. Combining chip-based technologies with genealogy data, we identified germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in individuals with pituitary adenoma predisposition (PAP). AIP acts in cytoplasmic retention of the latent form of the aryl hydrocarbon receptor and also has other functions. In a population-based series from Northern Finland, two AIP mutations account for 16% of all patients diagnosed with pituitary adenomas secreting growth hormone and for 40% of the subset of patients who were diagnosed when they were younger than 35 years of age. Typically, PAP patients do not display a strong family history of pituitary adenoma; thus, AIP is an example of a low-penetrance tumor susceptibility gene.