Low rate of germline AIP mutations in patients with apparently sporadic pituitary adenomas before the age of 40: a single-centre adult cohort.

To study the prevalence of germline mutations of the aryl-hydrocarbon receptor interacting protein (AIP) gene in a large cohort of patients seen in the Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM), UK, with apparently sporadic pituitary adenomas, who were either diagnosed or had relevant clinical manifestations by the age of 40 years. We prospectively investigated all patients who were seen at Oxford University Hospital, OCDEM, and a tertiary referral centre, between 2012 and 2013, and presented with pituitary tumours under the age of 40 years and with no family history: a total of 127 patients were enrolled in the study. Leukocyte-origin genomic DNA underwent sequence analysis of exons 1-6 and the flanking intronic regions of the AIP gene (NM_003977.2), with dosage analysis by multiplex ligation-dependent probe amplification. AIP variants were detected in 3% of the 127 patients, comprising four of 48 patients with acromegaly (8%), 0 of 43 with prolactinomas, 0 of the 20 patients with non-functioning adenomas, 0 of 15 with corticotroph adenomas and 0 of one with a thyrotroph adenomas. Definite pathogenetic mutations were seen in 2/4 variants, comprising 4.2% of patients with acromegaly. This prospective cohort study suggests a relatively low prevalence of AIP gene mutations in young patients with apparently sporadic pituitary adenomas presenting to a tertiary pituitary UK centre. Those with somatotroph macroadenomas have a higher rate of AIP mutation. These findings should inform discussion of genetic testing guidelines.

Preda V ，Korbonits M ，Cudlip S ，Karavitaki N ，Grossman AB ... -  《-》

Germline AIP mutations in apparently sporadic pituitary adenomas: prevalence in a prospective single-center cohort of 443 patients.

Cazabat L ，Bouligand J ，Salenave S ，Bernier M ，Gaillard S ，Parker F ，Young J ，Guiochon-Mantel A ，Chanson P ... -  《-》

Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas.

Georgitsi M ，De Menis E ，Cannavò S ，Mäkinen MJ ，Tuppurainen K ，Pauletto P ，Curtò L ，Weil RJ ，Paschke R ，Zielinski G ，Wasik A ，Lubinski J ，Vahteristo P ，Karhu A ，Aaltonen LA ... -  《-》

Very low frequency of germline GPR101 genetic variation and no biallelic defects with AIP in a large cohort of patients with sporadic pituitary adenomas.

Recently, germline and somatic GPR101 p.(E308D) mutation was found in patients with isolated acromegaly. It is not known whether GPR101 point mutations are associated with other histological types of pituitary adenoma. We sought germline GPR101 mutations in patients with sporadic pituitary adenomas, and compared the phenotypes of GPR101 mutation carriers and AIP mutation carriers. An observational cohort study performed between 2007 and 2014 in a single referral center. This prospective study involved 766 unselected patients (413 women) with sporadic pituitary adenomas of all histotypes. Entire GPR101 and AIP coding sequence were screened for germline mutations. Twelve patients (1.6%) were found to carry the GPR101 p.(E308D) mutation or rare GPR101 variants. The minor allele frequency of the GPR101 mutation and variants was higher in patients with pituitary adenomas than in unaffected individuals included in the Exome Aggregation Consortium database. Three of the six patients with the GPR101 p.(E308D) mutation had adult-onset acromegaly, two had adrenocorticotropin-secreting adenomas, and one had a nonfunctioning macroadenoma. Six patients carried rare GPR101 variants. Germline AIP mutations or rare AIP variants were identified in 32 patients (4.2%). AIP mutation carriers were younger at diagnosis than GPR101 mutation carriers and non carriers. None of the patients harbored mutations in both the GPR101 and AIP genes. Germline GPR101 mutations are very rare in patients with sporadic pituitary adenomas of various histotypes. No digenism with AIP was identified. Further studies are required to establish whether and how genetic variation in GPR101 gene contributes to pituitary tumorigenesis.

Lecoq AL ，Bouligand J ，Hage M ，Cazabat L ，Salenave S ，Linglart A ，Young J ，Guiochon-Mantel A ，Chanson P ，Kamenický P ... -  《-》

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis.

Cuny T ，Pertuit M ，Sahnoun-Fathallah M ，Daly A ，Occhi G ，Odou MF ，Tabarin A ，Nunes ML ，Delemer B ，Rohmer V ，Desailloud R ，Kerlan V ，Chabre O ，Sadoul JL ，Cogne M ，Caron P ，Cortet-Rudelli C ，Lienhardt A ，Raingeard I ，Guedj AM ，Brue T ，Beckers A ，Weryha G ，Enjalbert A ，Barlier A ... -  《-》