title: Genetic mutations in sporadic pituitary adenomas--what to screen for?
abstract: Pituitary adenomas are benign intracranial neoplasms that can result in morbidity owing to local invasion and/or excessive or deficient hormone production. The prevalence of symptomatic pituitary adenomas is approximately 1:1,000 in the general population. The vast majority of these tumours occur sporadically and are not part of syndromic disorders. However, germline mutations in genes known to predispose individuals to familial pituitary adenomas are found in a few patients with sporadic pituitary adenomas. Mutations in AIP (encoding aryl-hydrocarbon receptor-interacting protein) are the most frequently observed germline mutations. The prevalence of these mutations in patients with sporadic pituitary adenomas is ∼4%, but can increase to 8-20% in young adults with macroadenomas or gigantism, and also in children. Germline mutations in MEN1 (encoding menin) result in multiple endocrine neoplasia type 1 and are found in very young patients with isolated sporadic pituitary adenomas, which highlights the importance of the chromosome 11q13 locus in pituitary tumorigenesis. In this Review, we describe the clinical features of patients with sporadic pituitary adenomas that are associated with AIP or MEN1 mutations, and discuss the molecular mechanisms that might be involved in pituitary adenoma tumorigenesis. We also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations.
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction, AP-HP, Hôpitaux Universitaires Paris-Sud (site Bicêtre), 78 Rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Lecoq
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction, AP-HP, Hôpitaux Universitaires Paris-Sud (site Bicêtre), 78 Rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Kamenický
authors.affiliation: Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, AP-HP, Hôpitaux Universitaires Paris-Sud (site Bicêtre), 78 Rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction, AP-HP, Hôpitaux Universitaires Paris-Sud (site Bicêtre), 78 Rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000818:Animals; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; C103265:aryl hydrocarbon receptor-interacting protein