title: Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis.
abstract: BACKGROUND
  Germline mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) have been identified in young patients (age ≤30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of multiple endocrine neoplasia type 1 (MEN1) mutations in such a population.
  
  
  OBJECTIVE
  We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age ≤30 years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions.
  
  
  METHODS
  The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions.
  
  
  METHODS
  One hundred and seventy-four patients from endocrinology departments of 15 French University Hospital Centers were eligible for this study.
  
  
  RESULTS
  Twenty-one out of 174 (12%) patients had AIP (n=15, 8.6%) or MEN1 (n=6, 3.4%) mutations. In pediatric patients (age ≤18 years old), AIP/MEN1 mutation frequency reached nearly 22% (n=10/46). AIPmut and MEN1mut were identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients respectively; they each accounted for 4/74 (5.4%) prolactinoma (PRL) patients with mutations. Half of those patients (n=3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the eight corticotroph adenomas or the single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients.
  
  
  CONCLUSIONS
  Mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly PRL, and together with AIP, we suggest genetic analysis of MEN1 in such a population.
authors: Department of Endocrinology, University Hospital of Nancy-Brabois, 54500 Vandoeuvre-les-Nancy, France.
authors: Thomas
authors: T
authors: Cuny
authors: Morgane
authors: M
authors: Pertuit
authors: Mona
authors: M
authors: Sahnoun-Fathallah
authors: Adrian
authors: A
authors: Daly
authors: Gianluca
authors: G
authors: Occhi
authors: Marie Françoise
authors: MF
authors: Odou
authors: Antoine
authors: A
authors: Tabarin
authors: Marie Laure
authors: ML
authors: Nunes
authors: Brigitte
authors: B
authors: Delemer
authors: Vincent
authors: V
authors: Rohmer
authors: Rachel
authors: R
authors: Desailloud
authors: Véronique
authors: V
authors: Kerlan
authors: Olivier
authors: O
authors: Chabre
authors: Jean-Louis
authors: JL
authors: Sadoul
authors: Muriel
authors: M
authors: Cogne
authors: Philippe
authors: P
authors: Caron
authors: Christine
authors: C
authors: Cortet-Rudelli
authors: Anne
authors: A
authors: Lienhardt
authors: Isabelle
authors: I
authors: Raingeard
authors: Anne-Marie
authors: AM
authors: Guedj
authors: Thierry
authors: T
authors: Brue
authors: Albert
authors: A
authors: Beckers
authors: Georges
authors: G
authors: Weryha
authors: Alain
authors: A
authors: Enjalbert
authors: Anne
authors: A
authors: Barlier
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; C103265:aryl hydrocarbon receptor-interacting protein