Adenoma/genetics; Adolescent; Adult; Australia; DNA/chemistry/genetics; Female; Genetic Variation; Germ-Line Mutation; Humans; Intracellular Signaling Peptides and Proteins/genetics; Male; New Zealand; Pedigree; Pituitary Neoplasms/genetics; Point Mutation; Polynesia/ethnology; Sequence Analysis, DNA; Young Adult
Abstract :
[en] OBJECTIVE: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were recently shown to confer a pituitary adenoma predisposition in patients with familial isolated pituitary adenomas (FIPA). We report a large Samoan FIPA kindred from Australia/New Zealand with an R271W mutation that was associated with aggressive pituitary tumors. DESIGN AND METHODS: Case series with germline screening of AIP and haplotype analyses among R271W families. RESULTS: This previously unreported kindred consisted of three affected individuals that either presented with or had first symptoms of a pituitary macroadenoma in late childhood or adolescence. The index case, a 15-year-old male with incipient gigantism and his maternal aunt, had somatotropinomas, and the maternal uncle of the index case had a prolactinoma. All tumors were large (15, 40, and 60 mm maximum diameter) and two required transcranial surgery and radiotherapy. All three affected subjects and ten other unaffected relatives were found to be positive for a germline R271W AIP mutation. Comparison of the single nucleotide polymorphism patterns among this family and two previously reported European FIPA families with the same R271W mutation demonstrated no common ancestry. CONCLUSIONS: This kindred exemplifies the aggressive features of pituitary adenomas associated with AIP mutations, while genetic analyses among three R271W FIPA families indicate that R271W represents a mutational hotspot that should be studied further in functional studies.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Jennings, J. E.
Georgitsi, M.
Holdaway, I.
Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Tichomirowa, M.
Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Aaltonen, Lauri A
Karhu, A.
Cameron, F. J.
Language :
English
Title :
Aggressive pituitary adenomas occurring in young patients in a large Polynesian kindred with a germline R271W mutation in the AIP gene.
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA & Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. Journal of Clinical Endocrinology and Metabolism 2006 91 4769-4775. (Pubitemid 44917305)
Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML & McCutcheon IE. The prevalence of pituitary adenomas: a systematic review. Cancer 2004 101 613-619. (Pubitemid 38970613)
Besser GM, Burman P & Daly AF. Predictors and rates of treatment-resistant tumor growth in acromegaly. European Journal of Endocrinology 2005 153 187-193. (Pubitemid 41167474)
Asa SL & Ezzat S. Genetics and proteomics of pituitary tumors. Endocrine 2005 28 43-47.
Beckers A & Daly AF. The clinical, pathological, and genetic features of familial isolated pituitary adenomas. European Journal of Endocrinology 2007 157 371-382. (Pubitemid 350018439)
Daly AF, Jaffrain-Rea ML & Beckers A. Clinical and genetic features of familial pituitary adenomas. Hormone and Metabolic Research 2005 37 347-354. (Pubitemid 41008768)
Daly AF, Jaffrain-Rea ML, Ciccarelli A, Valdes-Socin H, Rohmer V, Tamburrano G, Borson-Chazot C, Estour B, Ciccarelli E, Brue T, Ferolla P, Emy P, Colao A, De Menis E, Lecomte P, Penfornis F, Delemer B, Bertherat J, Wemeau JL, De Herder W, Archambeaud F, Stevenaert A, Calender A, Murat A, Cavagnini F & Beckers A. Clinical characterization of familial isolated pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 2006 91 3316-3323. (Pubitemid 44402097)
Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A, Tuppurainen K, Ebeling TM, Salmela PI, Paschke R, Gundogdu S, De Menis E, Makinen MJ, Launonen V, Karhu A & Aaltonen LA. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006 312 1228-1230. (Pubitemid 43801151)
Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, Murat A, Emy P, Gimenez-Roqueplo AP, Tamburrano G, Raverot G, Barlier A, De Herder W, Penfornis A, Ciccarelli E, Estour B, Lecomte P, Gatta B, Chabre O, Sabate MI, Bertagna X, Garcia Basavilbaso N, Stalldecker G, Colao A, Ferolla P, Wemeau JL, Caron P, Sadoul JL, Oneto A, Archambeaud F, Calender A, Sinilnikova O, Montanana CF, Cavagnini F, Hana V, Solano A, Delettieres D, Luccio-Camelo DC, Basso A, Rohmer V, Brue T, Bours V, Teh BT & Beckers A. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. Journal of Clinical Endocrinology and Metabolism 2007 92 1891-1896. (Pubitemid 46997206)
Barlier A, Vanbellinghen JF, Daly AF, Silvy M, Jaffrain-Rea ML, Trouillas J, Tamagno G, Cazabat L, Bours V, Brue T, Enjalbert A & Beckers A. Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 2007 92 1952-1955. (Pubitemid 46997216)
Cazabat L, Libe R, Perlemoine K, Rene-Corail F, Burnichon N, Gimenez-Roqueplo AP, Dupasquier-Fediaevsky L, Bertagna X, Clauser E, Chanson P, Bertherat J & Raffin-Sanson ML. Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas. European Journal of Endocrinology 2007 157 1-8. (Pubitemid 47162559)
Georgitsi M, Raitila A, Karhu A, Tuppurainen K, Makinen MJ, Vierimaa O, Paschke R, Saeger W, van der Luijt RB, Sane T, Robledo M, De Menis E, Weil RJ, Wasik A, Zielinski G, Lucewicz O, Lubinski J, Launonen V, Vahteristo P & Aaltonen LA. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. PNAS 2007 104 4101-4105. (Pubitemid 47181585)
Iwata T, Yamada S, Mizusawa N, Golam HM, Sano T & Yoshimoto K. The aryl hydrocarbon receptor-interacting protein gene is rarely mutated in sporadic GH-secreting adenomas. Clinical Endocrinology 2007 66 499-502. (Pubitemid 46434927)
Naves LA, Daly AF, Vanbellinghen JF, Casulari LA, Spilioti C, Magalhaes AV, Azevedo MF, Giacomini LA, Nascimento PP, Nunes RO, Rosa JW, Jaffrain-Rea ML, Bours V & Beckers A. Variable pathological and clinical features of a large Brazilian family harboring a mutation in the aryl hydrocarbon receptor-interacting protein gene. European Journal of Endocrinology 2007 157 383-391. (Pubitemid 350018440)
Toledo RA, Lourenco DM Jr, Liberman B, Cunha-Neto MB, Cavalcanti MG, Moyses CB, Toledo SP & Dahia PL. Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. Journal of Clinical Endocrinology and Metabolism 2007 92 1934-1937. (Pubitemid 46997212)
Cazabat L, Guillaud-Bataille M, Bertherat J & Raffin-Sanson ML. Mutations of the gene for the aryl hydrocarbon receptor-interacting protein in pituitary adenomas. Hormone Research 2009 71 132-141.
Georgitsi M, Heliovaara E, Paschke R, Kumar AV, Tischkowitz M, Vierimaa O, Salmela P, Sane T, De Menis E, Cannavo S, Gundogdu S, Lucassen A, Izatt L, Aylwin S, Bano G, Hodgson S, Koch CA, Karhu A & Aaltonen LA. Large genomic deletions in AIP in pituitary adenoma predisposition. Journal of Clinical Endocrinology and Metabolism 2008 93 4146-4151.
Meyer BK, Petrulis JR & Perdew GH. Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90-associated immunophilin homolog XAP2. Cell Stress & Chaperones 2000 5 243-254.
Buchbinder S, Bierhaus A, Zorn M, Nawroth PP, Humpert P & Schilling T. Aryl hydrocarbon receptor interacting protein gene (AIP) mutations are rare in patients with hormone secreting or non-secreting pituitary adenomas. Experimental and Clinical Endocrinology & Diabetes 2008 116 625-628.
Bell DR & Poland A. Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role of hsp90. Journal of Biological Chemistry 2000 275 36407-36414. (Pubitemid 30841197)
Safe S. Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicology Letters 2001 120 1-7. (Pubitemid 32375066)
Carlson DB & Perdew GH. A dynamic role for the Ah receptor in cell signaling? Insights from a diverse group of Ah receptor interacting proteins Journal of Biochemical and Molecular Toxicology 2002 16 317-325.
de Oliveira SK, Hoffmeister M, Gambaryan S, Muller-Esterl W, Guimaraes JA & Smolenski AP. Phosphodiesterase 2A forms a complex with the co-chaperone XAP2 and regulates nuclear translocation of the aryl hydrocarbon receptor. Journal of Biological Chemistry 2007 282 13656-13663. (Pubitemid 47100556)
Vargiolu M, Fusco D, Kurelac I, Dirnberger D, Baumeister R, Morra I, Melcarne A, Rimondini R, Romeo G & Bonora E. The tyrosine kinase receptor RET interacts in vivo with AIP to alter survivin availability. Journal of Clinical Endocrinology and Metabolism 2009 94 2571-2578.
Yu R, Bonert V, Saporta I, Raffel LJ & Melmed S. Aryl hydrocarbon receptor interacting protein variants in sporadic pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 2006 91 5126-5129. (Pubitemid 44917362)
DiGiovanni R, Serra S, Ezzat S & Asa SL. AIP mutations are not identified in patients with sporadic pituitary adenomas. Endocrine Pathology 2007 18 76-78. (Pubitemid 47574990)
Georgitsi M, De Menis E, Cannavo S, Makinen MJ, Tuppurainen K, Pauletto P, Curto L, Weil RJ, Paschke R, Zielinski G, Wasik A, Lubinski J, Vahteristo P, Karhu A & Aaltonen LA. Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas. Clinical Endocrinology 2008 69 621-627.
Georgitsi M, Karhu A, Winqvist R, Visakorpi T, Waltering K, Vahteristo P, Launonen V & Aaltonen LA. Mutation analysis of aryl hydrocarbon receptor interacting protein (AIP) gene in colorectal, breast, and prostate cancers. British Journal of Cancer 2007 96 352-356. (Pubitemid 46160642)
Holdaway IM, Rajasoorya RC & Gamble GD. Factors influencing mortality in acromegaly. Journal of Clinical Endocrinology and Metabolism 2004 89 667-674.
