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Genetic Causes of Familial Pituitary Adenomas

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Growth Hormone Related Diseases and Therapy

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Pituitary adenomas are benign intracranial neoplasms and clinically apparent pituitary adenomas have a prevalence of approximately 1:1,000 individuals. They usually arise sporadically, but familial pituitary adenomas comprise about 5% of all cases, more than half of which include multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). The other half is represented by familial isolated pituitary adenomas (FIPA), a clinical entity described in the late 1990s. Recently, interest has been focused on the genetic pathophysiology of familial pituitary adenomas. MEN1 is due to mutations in MEN1 gene. CNC is related to PRKAR1A mutations and still unknown disruptions on 2p16. Mutations of CDKN1B in MEN1-like patients without MEN1 mutations allowed the differentiation of the condition as MEN4. About 15% of FIPA kindreds are associated with aryl hydrocarbon receptor-interacting protein (AIP) gene mutations, which suggests that this is a genetically heterogeneous condition. Overall, familial pituitary adenomas represent a small proportion of pituitary tumors, but are particularly significant as affected individuals may be younger, and adenomas may be relatively difficult to treat.

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References

  1. Ambrosi B, Faglia G. Epidemiology of pituitary tumors. In: Faglia G, Beck-Peccoz P, Ambrosi B, editors. Pituitary adenomas: new trends in basic and clinical research. Amsterdam: Elsevier; 1991. p. 159–68.

    Google Scholar 

  2. Clayton RN. Sporadic pituitary adenomas: from epidemiology to use of databases. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13:451–60.

    Article  PubMed  CAS  Google Scholar 

  3. Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101:613–9.

    Article  PubMed  Google Scholar 

  4. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a crosssectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006;91:4769–75.

    Article  PubMed  CAS  Google Scholar 

  5. Central Brain Tumor Registry of the United States 2007–2008. Central Brain Tumor Registry of the United States Statistical Report; 2008.

    Google Scholar 

  6. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86:5658–71.

    Article  PubMed  CAS  Google Scholar 

  7. Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954;16:363–71.

    Article  PubMed  CAS  Google Scholar 

  8. Erdheim J. Zur normalen und pathologischen Histologie der Glandula thyreoidiea, parathyroidea und Hypophysis. Beitr Pathol Anat. 1903;33:158–65.

    Google Scholar 

  9. Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988;332:85–7.

    Article  PubMed  CAS  Google Scholar 

  10. Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276:404–7.

    Article  PubMed  CAS  Google Scholar 

  11. Sayo Y, Murao K, Imachi H, Cao WM, Sato M, Dobashi H, et al. The multiple endocrine neoplasia type 1 gene product, menin, inhibits insulin production in rat insulinoma cells. Endocrinology. 2002;143:2437–40.

    Article  PubMed  CAS  Google Scholar 

  12. La P, Schnepp RW, Petersen D, Silva C, Hua X. Tumor suppressor menin regulates expression of insulin-like growth factor binding protein 2. Endocrinology. 2004;145:3443–50.

    Article  PubMed  CAS  Google Scholar 

  13. Namihira H, Sato M, Murao K, Cao WM, Matsubara S, Imachi H, et al. The multiple endocrine neoplasia type 1 gene product, menin, inhibits the human prolactin promoter activity. J Mol Endocrinol. 2002;29:297–304.

    Article  PubMed  CAS  Google Scholar 

  14. Scacheri PC, Davis S, Odom DT, Crawford GE, Perkins S, Halawi MJ, et al. Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet. 2006;2:e51.

    Article  PubMed  Google Scholar 

  15. Hughes CM, Rozenblatt-Rosen O, Milne TA, Copeland TD, Levine SS, Lee JC, et al. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Mol Cell. 2004;13:587–97.

    Article  PubMed  CAS  Google Scholar 

  16. Horvath A, Stratakis CA. Clinical and molecular genetics of acromegaly: MEN1, Carney complex, McCune–Albright syndrome, familial acromegaly and genetic defects in sporadic tumors. Rev Endocr Metab Disord. 2008;9:1–11.

    Article  PubMed  CAS  Google Scholar 

  17. Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S, Yaniv M. Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell. 1994;76:747–60.

    Article  PubMed  CAS  Google Scholar 

  18. Heppner C, Bilimoria KY, Agarwal SK, Kester M, Whitty LJ, Guru SC, et al. The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation. Oncogene. 2001;20:4917–25.

    Article  PubMed  CAS  Google Scholar 

  19. Kaji H, Canaff L, Lebrun JJ, Goltzman D, Hendy GN. Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling. Proc Natl Acad Sci U S A. 2001;98:3837–42.

    Article  PubMed  CAS  Google Scholar 

  20. Farid N, Buehler S, Russel N, Maroun F, Allerdice P, Smyth H. Prolactinomas in familial multiple endocrine neoplasia syndrome type I. Relationship to HLA and carcinoid tumors. Am J Med. 1980;69:874–80.

    Article  PubMed  CAS  Google Scholar 

  21. Scheithauer BW, Laws Jr ER, Kovacs K, Horvath E, Randall RV, Carney JA. Pituitary adenomas of the multiple endocrine neoplasia type I syndrome. Semin Diagn Pathol. 1987;4:205–11.

    PubMed  CAS  Google Scholar 

  22. Verges B, Boureille F, Goudet P, Murat A, Beckers A, Sassolas G, et al. Pituitary disease in MEN type 1 (MEN1): data from the France–Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87:457–65.

    Article  PubMed  CAS  Google Scholar 

  23. Poncin J, Stevenaert A, Beckers A. Somatic MEN1 gene mutations does not contribute significantly to sporadic pituitary tumorigenesis. Eur J Endocrinol. 1999;140:573–6.

    Article  PubMed  CAS  Google Scholar 

  24. Trouillas J, Labat-Moleur F, Sturm N, Kujas M, Heymann M-F, Figarella-Branger D, et al. Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol. 2008;32:534–43.

    Article  PubMed  Google Scholar 

  25. Olufemi SE, Green J, Manickam P, Guru SC, Agarwal SK, Kester M, et al. Common ancestral mutation in the MEN1 gene is likely responsible for the prolactinoma prolactinoma variant of MEN1 (MEN1Burin) in four kindreds from Newfoundland. Hum Mutat. 1998;11:264–9.

    Article  PubMed  CAS  Google Scholar 

  26. Burgess JR, Shepherd JJ, Parameswaran V, Hoffman L, Greenaway TM. Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred. J Clin Endocrinol Metab. 1996;81:2642–6.

    Article  PubMed  CAS  Google Scholar 

  27. Bertolinio P, Tong WM, Galendo D, Wang ZQ, Zhang CX. Heterozygous MEN1 mutant mice develop a range of endocrine tumors mimicking multiple endocrine neoplasia type 1. Mol Endocrinol. 2003;17:1880–92.

    Article  Google Scholar 

  28. Bertolinio P, Radanovic I, Casse H, Aguzzi A, Wang ZQ, Zhang CX. Genetic ablation of the tumor suppressor menin causes lethality at mid-gestation with defects in multiple organs. Mech Dev. 2003;120:549–60.

    Article  Google Scholar 

  29. Biondi CA, Garside MG, Waring P, Loffler KA, Stark MS, Magnuson MA, et al. Conditional inactivation of the MEN1 gene leads to pancreatic and pituitary tumorigenesis but does not affect normal development of these tissues. Mol Cell Biol. 2004;24:3125–31.

    Article  PubMed  CAS  Google Scholar 

  30. Hai N, Aoki N, Shimatsu A, Mod T, Kosugi S. Clinical features of multiple endocrine neoplasia type 1 (MEN1) phenocopy without germline MEN1 gene mutations: analysis of 20 Japanese sporadic casis with MEN1. Clin Endocrinol. 2000;52:509–18.

    Article  CAS  Google Scholar 

  31. Fritz A, Walch A, Piotrowska K, et al. Recessive transmission of a multiple endocrine neoplasia syndrome in the rat. Cancer Res. 2002;62:3048–51.

    PubMed  CAS  Google Scholar 

  32. Piotrowska K, Pellegata NS, Rosemann M, Fritz A, Graw J, Atkinson MJ. Mapping of a novel MEN-like syndrome locus to rat chromosome 4. Mamm Genome. 2004;15:135–41.

    Article  PubMed  Google Scholar 

  33. Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006;103:15558–63.

    Article  PubMed  CAS  Google Scholar 

  34. Quereda V, Malumbres M. Cell cycle control of the pituitary. J Mol Endocrinol. 2009;42:75–86.

    Article  PubMed  CAS  Google Scholar 

  35. Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, et al. Mice lacking p27Kip1 display increased body size, multiple organ hyperplasia, retinal dysplasia and pituitary tumors. Cell. 1996;85:707–20.

    Article  PubMed  CAS  Google Scholar 

  36. Kiyokawa H, Kineman RD, Manova-Todorova KO, Soares VC, Hoffman ES, et al. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1. Cell. 1996;85:721–32.

    Article  PubMed  CAS  Google Scholar 

  37. Jin L, Qian X, Kulig E, et al. Transforming growth factor-beta, transforming growth factor-beta receptor II and p27Kip1 expression in nontumorous and neoplastic human pituitaries. Am J Pathol. 1997;151:509–19.

    PubMed  CAS  Google Scholar 

  38. Bamberger CM, Fehn M, Bamberger AM, et al. Reduced expression levels of the cell-cycle inhibitor p27Kip1 in human pituitary adenomas. Eur J Endocrinol. 1999;140:250–5.

    Article  PubMed  CAS  Google Scholar 

  39. Drosten M, Hilken G, Bockmann M, Rodicker F, Mise N, Cranston AN, et al. Role of MEN2A-derived RET in maintenance and proliferation of medullary thyroid carcinoma. J Natl Cancer Inst. 2004;96:1231–9.

    Article  PubMed  CAS  Google Scholar 

  40. Kolluri SK, Weiss C, Koff A, Gottlicher M. p27Kip1 induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Genes Dev. 1999;13:1742–53.

    Article  PubMed  CAS  Google Scholar 

  41. Georgitsi M, Raitila A, Karhu A, van der Lujit RB, Aalfs CM, Sane T, et al. Germline CDKN1B/p27kip1 mutation in multiple endocrine neoplasia. J Clin Endocrinol Metab. 2007;92:3321–5.

    Article  PubMed  CAS  Google Scholar 

  42. Agarwal SK, Mateo CM, Marx SJ. Rare germline mutations in cyclin-dependent kinase inhibitor genes in MEN1 and related states. J Clin Endocrinol Metab. 2009;94:1826–34.

    Article  PubMed  CAS  Google Scholar 

  43. Igreja SC, Chahal HS, Akker SA, Gueorguiev M, Popovic V, Damjanovic S, et al. Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and AIP (aryl hydrocarbon receptor-interacting protein) genes in MEN1 syndrome patients without any detectable MEN1gene mutations. Clin Endocrinol. 2009;70:259–64.

    Article  CAS  Google Scholar 

  44. Stratakis CA, Bertherat J, Carney JA. Mutation of perinatal myosin heavy chain. N Engl J Med. 2004;351:2556–8.

    Article  PubMed  CAS  Google Scholar 

  45. Bain F. Carney complex [letter to editor]. Mayo Clin Proc. 1986;61:508.

    PubMed  CAS  Google Scholar 

  46. Boikos SA, Stratakis CA. Carney complex: the first 20 years. Curr Opin Oncol. 2007;19:24–9.

    Article  PubMed  CAS  Google Scholar 

  47. Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet. 2000;26:89–92.

    Article  PubMed  CAS  Google Scholar 

  48. Kaltsas GA, Kola B, Borboli N, Morris DG, Gueorguiev M, Swords FM, et al. Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours. Clin Endocrinol (Oxf). 2002;57:443–8.

    Article  CAS  Google Scholar 

  49. Sandrini F, Kirschner LS, Bei T, Farmakidis C, Yasufuku-Takano J, Takano K, et al. PRKAR1A, one of the Carney complex genes, and its locus (17q22-24) are rarely altered in pituitary tumours outside the Carney complex. J Med Genet. 2002;39:e78.

    Article  PubMed  CAS  Google Scholar 

  50. Bossis I, Stratakis CA. PRKAR1A: normal and abnormal functions. Endocrinology. 2004;145:5452–8.

    Article  PubMed  CAS  Google Scholar 

  51. Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Investig. 1996;97:699–705.

    Article  PubMed  CAS  Google Scholar 

  52. Boikos SA, Stratakis CA. Pituitary pathology in patients with Carney complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities. Pituitary. 2006;9:203–9.

    Article  PubMed  CAS  Google Scholar 

  53. Pack SD, Kirschner LS, Pak E, Zhuang Z, Carney JA, Stratakis CA. Genetic and histological studies of somatomammotropic tumors in patients with the ‘Complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas’ (Carney complex). J Clin Endocrinol Metab. 2000;85:3860–5.

    Article  PubMed  CAS  Google Scholar 

  54. Kurtkaya-Yapicier O, Scheithauer B, Carney JA, et al. Pituitary adenoma in Carney complex: an immunohistochemical, ultrastructural, and immunoelectron microscopic study. Ultrastruct Pathol. 2002;26:345–53.

    Article  PubMed  CAS  Google Scholar 

  55. Griffin KJ, Kirschner LS, Matyakhina L, Stergiopoulos SG, Robinson-White A, Lenherr SM, et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet. 2004;41:923–31.

    Article  PubMed  CAS  Google Scholar 

  56. Griffin KJ, Kirschner LS, Matyakhina L, Stergiopoulos S, Robinson-White A, Lenherr S, et al. Down-regulation of regulatory subunit type 1A of protein kinase A leads to endocrine and other tumors. Cancer Res. 2004;64:8811–5.

    Article  PubMed  CAS  Google Scholar 

  57. Yin Z, Williams-Simons L, Parlow AF, Asa S, Kirschner LS. Pituitary-specific knockout of the Carney complex gene PRKAR1A leads to pituitary tumorigenesis. Mol Endocrinol. 2008;22:380–7.

    Article  PubMed  CAS  Google Scholar 

  58. Bailey P, Cushing H. The microscopic structure of the adenomas in acromegalic dyspituitarism (fugitive acromegaly). Am J Pathol. 1928;4:545–63.

    PubMed  CAS  Google Scholar 

  59. Daly AF, Jaffrain-Rea ML, Ciccarelli A, Valdes-Socin H, Rohmer V, Tamburrano G, et al. Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab. 2006;91:3316–23.

    Article  PubMed  CAS  Google Scholar 

  60. Verloes A, Stevenaert A, Teh BT, Petrossians P, Beckers A. Familial acromegaly: case report and review of the literature. Pituitary. 1999;1:273–7.

    Article  PubMed  CAS  Google Scholar 

  61. Frohman LA, Eguchi K. Familial acromegaly. Growth Horm IGF Res. 2004;14:S90–6.

    Article  PubMed  CAS  Google Scholar 

  62. Beckers A, Daly A. The clinical, pathological, and genetic features of familial isolated pituitary adenomas. Eur J Endocrinol. 2007;157:371–82.

    Article  PubMed  CAS  Google Scholar 

  63. Teh BT, Kytola S, Farnebo F, Bergman L, Wong FK, Weber G, et al. Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism. J Clin Endocrinol Metab. 1998;83:2621–6.

    Article  PubMed  CAS  Google Scholar 

  64. Gadelha MR, Une KN, Rohde K, Vaisman M, Kineman RD, Frohman LA. Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12. J Clin Endocrinol Metab. 2000;85:707–14.

    Article  PubMed  CAS  Google Scholar 

  65. Luccio-Camelo DC, Une KN, Ferreira RE, Khoo SK, Nickolov R, Bronstein MD, et al. A meiotic recombination in a new isolated familial somatotropinoma kindred. Eur J Endocrinol. 2004;150:643–8.

    Article  PubMed  CAS  Google Scholar 

  66. Linquette M, Herlant M, Laine E, Fossati P, Dupont-Lecompte J. Adenome a prolactine chez une jeune fine dont la mere etait porteuse d’un adenome hypophysaire avec amenorrhee galactorrhee. Ann Endocrinol. 1997;28:773–80.

    Google Scholar 

  67. Berezin M, Karasik A. Familial prolactinoma. Clin Endocrinol. 1995;42:483–6.

    Article  CAS  Google Scholar 

  68. Salti IS, Mufarrij IS. Familial Cushing disease. Am J Med Genet. 1981;8:91–4.

    Article  PubMed  CAS  Google Scholar 

  69. Yuasa H, Tokito S, Nakagaki H, Kitamura K. Familial pituitary adenoma – report of four cases from two unrelated families. Neurol Med Chir (Tokyo). 1990;30:1016–9.

    Article  CAS  Google Scholar 

  70. Valdes-Socin H, Poncin J, Stevens V, Stevenaert A, Beckers A. Adenomes hypophysaires familiaux isoles non lies avec la mutation somatique NEM-1. Suivi de 27 patients. Ann Endocrinol. 2000;61:301.

    Google Scholar 

  71. Valdes-Socin H, Jaffrain Rea ML, Tamburrano G, Cavagnini F, Ciccarelli A, Colao A, et al. Familial isolated pituitary tumors: clinical and molecular studies in 80 patients. In: Endocrine Society’s 84th Annual Meeting; 2002. P3-663 647.

    Google Scholar 

  72. Beckers A. Familial isolated pituitary adenomas. The Ninth International Workshop on multiple endocrine neoplasia (MEN2004). J Intern Med. 2004;255:696–730.

    Article  Google Scholar 

  73. Daly AF, Tichomirowa MA, Beckers A. Genetic, molecular and clinical features of familial isolated pituitary adenomas. Horm Res. 2009;71 Suppl 2:116–22.

    Article  PubMed  CAS  Google Scholar 

  74. Leontiou CA, Gueorguiev M, van der Spuy J, Quinton R, Lolli F, Hassan S, et al. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J Clin Endocrinol Metab. 2008;93:2390–401.

    Article  PubMed  CAS  Google Scholar 

  75. Villa C, Magri F, Morbini P, et al. Silent familial isolated pituitary adenomas: histopathological and clinical case report. Endocr Pathol. 2008;19:40–6.

    Article  PubMed  CAS  Google Scholar 

  76. Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science. 2006;312:1228–30.

    Article  PubMed  CAS  Google Scholar 

  77. Yu R, Bonert V, Saporta I, Raffel LJ, Melmed S. Aryl hydrocarbon receptor interacting protein variants in sporadic pituitary adenomas. J Clin Endocrinol Metab. 2006;91:5126–9.

    Article  PubMed  CAS  Google Scholar 

  78. Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, et al. Aryl hydrocarbon receptorinteracting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab. 2007;92:1891–6.

    Article  PubMed  CAS  Google Scholar 

  79. Barlier A, Vanbellinghen JF, Daly AF, Silvy M, Jaffrain-Rea ML, Trouillas J, et al. Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas. J Clin Endocrinol Metab. 2007;92:1952–5.

    Article  PubMed  CAS  Google Scholar 

  80. Toledo RA, Lourenco Jr DM, Liberman B, Cunha-Neto MB, Cavalcanti MG, Moyses CB, et al. Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. J Clin Endocrinol Metab. 2007;92:1934–7.

    Article  PubMed  CAS  Google Scholar 

  81. 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. Clin Endocrinol. 2007;66:499–502.

    CAS  Google Scholar 

  82. Georgitsi M, Raitila A, Karhu A, Tuppurainen K, Makinen MJ, Vierimaa O, et al. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. Proc Natl Acad Sci U S A. 2007;104:4101–5.

    Article  PubMed  CAS  Google Scholar 

  83. Georgitsi M, Karhu A, Winqvist R, Visakorpi T, Waltering K, Vahteristo P, et al. Mutation analysis of aryl hydrocarbon receptor interacting protein (AIP) gene in colorectal, breast, and prostate cancers. Br J Cancer. 2007;96:352–6.

    Article  PubMed  CAS  Google Scholar 

  84. Cazabat L, Libe R, Perlemoine K, Rene-Corail F, Burnichon N, Gimenez-Roquiplo AP, et al. 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. Eur J Endocrinol. 2007;157:1–8.

    Article  PubMed  CAS  Google Scholar 

  85. Tichomirowa MA, Daly AF, Pujol J, Naves LA, Rodien P, Vanbellinghen JF, et al. An analysis of the role of cyclin dependent kinase inhibitor 1B (CDKN1B) gene mutations in 86 families with familial isolated pituitary adenomas (FIPA). In: The Endocrine Society’s 91st Annual Meeting, 10–13 June, Washington; 2009.

    Google Scholar 

  86. Carver LA, LaPress JJ, Dunham EE, Bradfield CA. Characterization of the Ahreceptor-associated protein, ARA9. J Biol Chem. 1998;273:33580–7.

    Article  PubMed  CAS  Google Scholar 

  87. Bell DR, Poland A. Binding of aryl hydrocarbon receptor (AhR) to AhR-ineracting protein. The role of hsp90. J Biol Chem. 2000;275:36407–14.

    Article  PubMed  CAS  Google Scholar 

  88. Tichomirowa MA, Daly AF, Beckers A. Familial pituitary adenomas. J Intern Med. 2009;266:5–18.

    Article  PubMed  CAS  Google Scholar 

  89. Carver LA, Bradfield CA. Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo. J Biol Chem. 1997;272:11452–6.

    Article  PubMed  CAS  Google Scholar 

  90. Oesch-Bartlomowicz B, Oesch F. Role of cAMP in mediating AHR signaling. Biochem Pharmacol. 2009;77:627–41.

    Article  PubMed  CAS  Google Scholar 

  91. Lees MJ, Peet DJ, Whitelaw ML. Defining the role of XAP2 in stabilization of dioxin receptor. J Biol Chem. 2003;278:35878–88.

    Article  PubMed  CAS  Google Scholar 

  92. Bolger GB, Peden AH, Steele MR, MacKenzie C, McEwan DG, Wallace DA, et al. Attenuation of the activity of the cAMP-specific phosphodiesterasePDE4A5 by interaction with the immunophilin XAP2. J Biol Chem. 2003;278:33351–63.

    Article  PubMed  CAS  Google Scholar 

  93. 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. J Biol Chem. 2007;282:13656–63.

    Article  PubMed  Google Scholar 

  94. Jaffrain-Rea ML, Angelini M, Gargano D, Tichomirowa MA, Daly AF, Vanbellinghen JF, et al. Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications. Endocr Relat Cancer. 2009;16:1029–43.

    Article  PubMed  CAS  Google Scholar 

  95. Lin BC, Sullivan R, Lee Y, Moran S, Glover E, Bradfield CA. Deletion of the aryl hydrocarbon receptor-associated protein 9 leads to cardiac malformation and embryonic lethality. J Biol Chem. 2007;282:35924–32.

    Article  PubMed  CAS  Google Scholar 

  96. Lin BC, Nguyen LP, Walisser JA, Bradfield CA. A hypomorphic allele of aryl hydrocarbon receptor-associated protein-9 produces a phenocopy of the AHR-null mouse. Mol Pharmacol. 2008;74:1367–71.

    Article  PubMed  CAS  Google Scholar 

  97. Naves LA, Daly AF, Vanbellinghen JF, Casulari LA, Spilioti C, Magalhaes AV, et al. Variable pathological and clinical features of a large Brazilian family harboring a mutation in the aryl hydrocarbon receptor-interacting protein gene. Eur J Endocrinol. 2007;157:383–91.

    Article  PubMed  CAS  Google Scholar 

  98. Daly AF., Tichomirowa MA, Petrossians P, Heliövaara E, Jaffrain-Rea ML, Barlier A, et al.Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. The Journal of Clinical Endocrinology and Metabolism. 2010;95(11):E373–83.

    Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, C.H.U. de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium

    Silvia Vandeva

  2. Clinical Center of Endocrinology and Gerontology, Medical University Sofia, Sofia, Bulgaria

    Silvia Vandeva & Sabina Zacharieva

  3. Department of Endocrinology, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium

    Adrian F. Daly

  4. Department of Endocrinology, C.H.U. de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium

    Albert Beckers

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  3. Adrian F. Daly
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  4. Albert Beckers
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Correspondence to Albert Beckers .

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  1. Princess Alexandra Hospital &, The University of Queensland, Centres for Health Research, Ipswich Road Woolloongabba 199, Brisbane, 4102, Queensland, Australia

    Ken Ho

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Vandeva, S., Zacharieva, S., Daly, A.F., Beckers, A. (2011). Genetic Causes of Familial Pituitary Adenomas. In: Ho, K. (eds) Growth Hormone Related Diseases and Therapy. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-60761-317-6_7

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  • DOI: https://doi.org/10.1007/978-1-60761-317-6_7

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