Pituitary Adenoma Predisposition Caused by Germline Mutations in the AIP Gene
Outi Vierimaa,1*
Marianthi Georgitsi,3*
Rainer Lehtonen,3
Pia Vahteristo,3
Antti Kokko,3
Anniina Raitila,3
Karoliina Tuppurainen,4
Tapani M. L. Ebeling,2
Pasi I. Salmela,2
Ralf Paschke,5
Sadi Gündogdu,6
Ernesto De Menis,7
Markus J. Mäkinen,4
Virpi Launonen,3
Auli Karhu,3
Lauri A. Aaltonen3
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.
1 Department of Clinical Genetics, Oulu University Hospital, 90029 Oulu, Finland.
2 Department of Internal Medicine, Oulu University Hospital, 90029 Oulu, Finland.
3 Department of Medical Genetics, Molecular and Cancer Biology Research Program, 00014 University of Helsinki, Helsinki, Finland.
4 Department of Pathology, University of Oulu, 90014 Oulu, Finland.
5 Medical Department III, Leipzig University, 04103 Leipzig, Germany.
6 Division of Endocrinology-Metabolism and Diabetes, Cerrahpa
a Medical Faculty, University of Istanbul, 34303 Istanbul, Turkey.
7 Department of Internal Medicine, General Hospital, 31100 Treviso, Italy.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: lauri.aaltonen{at}helsinki.fi
