title: AIP Mutations are not identified in patients with sporadic pituitary adenomas.
abstract: The pathogenesis of pituitary adenomas remains a subject of interest. Recently, mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were identified as germline events leading to pituitary tumor predisposition in Finnish and Italian families with familial growth hormone-secreting pituitary adenomas and acromegaly. We examined the frequency of AIP mutations in pituitary tumors and blood of Canadian patients with sporadic pituitary somatotroph adenomas and sporadic pituitary adenomas of other types. Genomic DNA was extracted from pituitary tumors and white blood cells obtained from peripheral blood. Three PCR reactions were carried out to amplify the sites of known mutation, and amplified products were sequenced. AIP mutations were not detected as germline events in blood or as somatic alterations in tumors of 66 patients with pituitary adenomas. These included 50 acromegalics and 16 patients with other types of pituitary tumor. No mutations were detected in the blood of 22 controls and 10 patients with other endocrinopathies. Our results indicate that mutations in AIP are not identified in sporadic pituitary adenomas of Canadian patients. This rare mechanism of pituitary tumorigenesis appears to be unique to the initial Finnish and Italian families described.
authors.affiliation: Department of Pathology, University Health Network & Toronto Medical Laboratories, Ontario Cancer Institute, Toronto, Ontario, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: DiGiovanni
authors.forename: Stefano
authors.initials: S
authors.lastname: Serra
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
mesh_terms: D000172:Acromegaly / Q000209:etiology; D000236:Adenoma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010911:Pituitary Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D004247:DNA