title: Genetic analysis in a patient presenting with meningioma and familial isolated pituitary adenoma (FIPA) reveals selective involvement of the R81X mutation of the AIP gene in the pathogenesis of the pituitary tumor.
abstract: Familial isolated pituitary adenoma (FIPA), defined as the occurrence of at least two cases of pituitary adenoma in a family that does not exhibit features of syndromic diseases, such as Carney complex or Multiple Endocrine Neoplasia type 1 or 4, is a rare autosomal dominant disease with low penetrance. About 20 % of the families with FIPA harbor inactivating mutation in aryl hydrocarbon receptor-interacting protein gene (AIP) associated with loss of heterozygosity of the same genetic locus (11q13) in the tumor. Rarely different types of extra-pituitary tumors have been described in the setting of AIP mutation-positive FIPA. We present the case of a patient who was diagnosed with acromegaly due to the AIP mutation c.241C>T (p.R81X) at the age of 34 years, and treated by transsphenoidal surgery. At the age of 43 years she was diagnosed with a meningioma, and at age 46 had recurrence of the somatotropinoma. Genetic studies demonstrated loss of the normal allele (by sequencing and microsatellite analysis) in DNA from the pituitary adenoma but not from the meningioma, suggesting a selective involvement of AIP mutation in the pathogenesis of the pituitary adenoma, and a casual association with the meningioma. Further investigations are required to define the exact role of AIP in non-pituitary tumorigenesis.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University of Turin, 10126, Turin, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Guaraldi
authors.forename: Valentina
authors.initials: V
authors.lastname: Corazzini
authors.forename: Gary L
authors.initials: GL
authors.lastname: Gallia
authors.forename: Silvia
authors.initials: S
authors.lastname: Grottoli
authors.forename: Karen
authors.initials: K
authors.lastname: Stals
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Dalantaeva
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Frohman
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
mesh_terms: D000328:Adult; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D009154:Mutation; D010911:Pituitary Neoplasms / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein