TY - JOUR
T1 - Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas
T2 - Analysis in 73 families
AU - Daly, Adrian F.
AU - Vanbellinghen, Jean François
AU - Sok, Kean Khoo
AU - Jaffrain-Rea, Marie Lise
AU - Naves, Luciana A.
AU - Guitelman, Mirtha A.
AU - Murat, Arnaud
AU - Emy, Philippe
AU - Gimenez-Roqueplo, Anne Paule
AU - Tamburrano, Guido
AU - Raverot, Gérald
AU - Barlier, Anne
AU - De Herder, Wouter
AU - Penfornis, Alfred
AU - Ciccarelli, Enrica
AU - Estour, Bruno
AU - Lecomte, Pierre
AU - Gatta, Blandine
AU - Chabre, Olivier
AU - Sabaté, María Isabel
AU - Bertagna, Xavier
AU - Basavilbaso, Natalia Garcia
AU - Stalldecker, Graciela
AU - Colao, Annamaria
AU - Ferolla, Piero
AU - Wémeau, Jean Louis
AU - Caron, Philippe
AU - Sadoul, Jean Louis
AU - Oneto, Adriana
AU - Archambeaud, Françoise
AU - Calender, Alain
AU - Sinilnikova, Olga
AU - Montañana, Carmen Fajardo
AU - Cavagnini, Francesco
AU - Hana, Vaclav
AU - Solano, Angela
AU - Delettieres, Dreanina
AU - Luccio-Camelo, Douglas C.
AU - Basso, Armando
AU - Rohmer, Vincent
AU - Brue, Thierry
AU - Bours, Vincent
AU - Bin, Tean Teh
AU - Beckers, Albert
PY - 2007/5
Y1 - 2007/5
N2 - Context: An association between germline aryl hydrocarbon receptor-interacting protein (AIP) gene mutations and pituitary adenomas was recently shown. Objective: The objective of the study was to assess the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA). Design: This was a multicenter, international, collaborative study. Setting: The study was conducted in 34 university endocrinology and genetics departments in nine countries. Patients: Affected members from each FIPA family were studied. Relatives of patients with AIP mutations underwent AIP sequence analysis. Main Outcome Measures: Presence/absence and description of AIP gene mutations were the main outcome measures. Intervention: There was no intervention. Results: Seventy-three FIPA families were identified, with 156 patients with pituitary adenomas; the FIPA cohort was evenly divided between families with homogeneous and heterogeneous tumor expression. Eleven FIPA families had 10 germline AIP mutations. Nine mutations, R16H, G47_R54del, Q142X, E174frameshift, Q217X, Q239X, K241E, R271W, and Q285frameshift, have not been described previously. Tumors were significantly larger (P = 0.0005) and diagnosed at a younger age (P = 0.0006) in AIP mutation-positive vs. mutation-negative subjects. Somatotropinomas predominated among FIPA families with AIP mutations, but mixed GH/prolactin-secreting tumors, prolactinomas, and nonsecreting adenomas were also noted. Approximately 85% of the FIPA cohort and 50% of those with familial somatotropinomas were negative for AIP mutations. Conclusions: AIP mutations, of which nine new mutations have been described here, occur in approximately 15% of FIPA families. Although pituitary tumors occurring in association with AIP mutations are predominantly somatotropinomas, other tumor types are also seen. Further study of the impact of AIP mutations on protein expression and activity is necessary to elucidate their role in pituitary tumorigenesis in FIPA.
AB - Context: An association between germline aryl hydrocarbon receptor-interacting protein (AIP) gene mutations and pituitary adenomas was recently shown. Objective: The objective of the study was to assess the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA). Design: This was a multicenter, international, collaborative study. Setting: The study was conducted in 34 university endocrinology and genetics departments in nine countries. Patients: Affected members from each FIPA family were studied. Relatives of patients with AIP mutations underwent AIP sequence analysis. Main Outcome Measures: Presence/absence and description of AIP gene mutations were the main outcome measures. Intervention: There was no intervention. Results: Seventy-three FIPA families were identified, with 156 patients with pituitary adenomas; the FIPA cohort was evenly divided between families with homogeneous and heterogeneous tumor expression. Eleven FIPA families had 10 germline AIP mutations. Nine mutations, R16H, G47_R54del, Q142X, E174frameshift, Q217X, Q239X, K241E, R271W, and Q285frameshift, have not been described previously. Tumors were significantly larger (P = 0.0005) and diagnosed at a younger age (P = 0.0006) in AIP mutation-positive vs. mutation-negative subjects. Somatotropinomas predominated among FIPA families with AIP mutations, but mixed GH/prolactin-secreting tumors, prolactinomas, and nonsecreting adenomas were also noted. Approximately 85% of the FIPA cohort and 50% of those with familial somatotropinomas were negative for AIP mutations. Conclusions: AIP mutations, of which nine new mutations have been described here, occur in approximately 15% of FIPA families. Although pituitary tumors occurring in association with AIP mutations are predominantly somatotropinomas, other tumor types are also seen. Further study of the impact of AIP mutations on protein expression and activity is necessary to elucidate their role in pituitary tumorigenesis in FIPA.
UR - http://www.scopus.com/inward/record.url?scp=34249844835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249844835&partnerID=8YFLogxK
U2 - 10.1210/jc.2006-2513
DO - 10.1210/jc.2006-2513
M3 - Article
C2 - 17244780
AN - SCOPUS:34249844835
VL - 92
SP - 1891
EP - 1896
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -