High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas

Maria A. Tichomirowa, Anne Barlier, Adrian F. Daly, Marie Lise Jaffrain-Rea, Cristina Ronchi, Maria Yaneva, Jonathan D. Urban, Patrick Petrossians, Atanaska Elenkova, Antoine Tabarin, Rachel Desailloud, Dominique Maiter, Thomas Schürmeyer, Renato Cozzi, Marily Theodoropoulou, Caroline Sievers, Ignacio Bernabeu, Luciana A. Naves, Olivier Chabre, Carmen Fajardo Montañana & 14 others Vaclav Hana, Georges Halaby, Brigitte Delemer, José Ignacio Labarta Aizpún, Emmanuel Sonnet, Ángel Ferrandez Longás, Marie Thérèse Hagelstein, Philippe Caron, Günter K. Stalla, Vincent Bours, Sabina Zacharieva, Anna Spada, Thierry Brue, Albert Beckers

Research output: Contribution to journalArticle

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Abstract

Background: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. Methods: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. Results: Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. Conclusion: Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

Original languageEnglish
Pages (from-to)509-515
Number of pages7
JournalEuropean Journal of Endocrinology
Volume165
Issue number4
DOIs
Publication statusPublished - Oct 2011

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Mutation
Genes
Pituitary Neoplasms
Germ-Line Mutation
Pediatrics
Prolactinoma
Multiplex Polymerase Chain Reaction
Population
Referral and Consultation
Phenotype

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Tichomirowa, M. A., Barlier, A., Daly, A. F., Jaffrain-Rea, M. L., Ronchi, C., Yaneva, M., ... Beckers, A. (2011). High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas. European Journal of Endocrinology, 165(4), 509-515. https://doi.org/10.1530/EJE-11-0304

High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas. / Tichomirowa, Maria A.; Barlier, Anne; Daly, Adrian F.; Jaffrain-Rea, Marie Lise; Ronchi, Cristina; Yaneva, Maria; Urban, Jonathan D.; Petrossians, Patrick; Elenkova, Atanaska; Tabarin, Antoine; Desailloud, Rachel; Maiter, Dominique; Schürmeyer, Thomas; Cozzi, Renato; Theodoropoulou, Marily; Sievers, Caroline; Bernabeu, Ignacio; Naves, Luciana A.; Chabre, Olivier; Montañana, Carmen Fajardo; Hana, Vaclav; Halaby, Georges; Delemer, Brigitte; Labarta Aizpún, José Ignacio; Sonnet, Emmanuel; Ferrandez Longás, Ángel; Hagelstein, Marie Thérèse; Caron, Philippe; Stalla, Günter K.; Bours, Vincent; Zacharieva, Sabina; Spada, Anna; Brue, Thierry; Beckers, Albert.

In: European Journal of Endocrinology, Vol. 165, No. 4, 10.2011, p. 509-515.

Research output: Contribution to journalArticle

Tichomirowa, MA, Barlier, A, Daly, AF, Jaffrain-Rea, ML, Ronchi, C, Yaneva, M, Urban, JD, Petrossians, P, Elenkova, A, Tabarin, A, Desailloud, R, Maiter, D, Schürmeyer, T, Cozzi, R, Theodoropoulou, M, Sievers, C, Bernabeu, I, Naves, LA, Chabre, O, Montañana, CF, Hana, V, Halaby, G, Delemer, B, Labarta Aizpún, JI, Sonnet, E, Ferrandez Longás, Á, Hagelstein, MT, Caron, P, Stalla, GK, Bours, V, Zacharieva, S, Spada, A, Brue, T & Beckers, A 2011, 'High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas', European Journal of Endocrinology, vol. 165, no. 4, pp. 509-515. https://doi.org/10.1530/EJE-11-0304
Tichomirowa, Maria A. ; Barlier, Anne ; Daly, Adrian F. ; Jaffrain-Rea, Marie Lise ; Ronchi, Cristina ; Yaneva, Maria ; Urban, Jonathan D. ; Petrossians, Patrick ; Elenkova, Atanaska ; Tabarin, Antoine ; Desailloud, Rachel ; Maiter, Dominique ; Schürmeyer, Thomas ; Cozzi, Renato ; Theodoropoulou, Marily ; Sievers, Caroline ; Bernabeu, Ignacio ; Naves, Luciana A. ; Chabre, Olivier ; Montañana, Carmen Fajardo ; Hana, Vaclav ; Halaby, Georges ; Delemer, Brigitte ; Labarta Aizpún, José Ignacio ; Sonnet, Emmanuel ; Ferrandez Longás, Ángel ; Hagelstein, Marie Thérèse ; Caron, Philippe ; Stalla, Günter K. ; Bours, Vincent ; Zacharieva, Sabina ; Spada, Anna ; Brue, Thierry ; Beckers, Albert. / High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas. In: European Journal of Endocrinology. 2011 ; Vol. 165, No. 4. pp. 509-515.
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title = "High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas",
abstract = "Background: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. Methods: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. Results: Overall, 19/163 (11.7{\%}) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5{\%}) pediatric patients. Ten AIPmut were identified in 11/83 (13.3{\%}) sporadic somatotropinoma patients, in 7/61 (11.5{\%}) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. Conclusion: Germline AIPmut occur in 11.7{\%} of patients <30 years with sporadic pituitary macroadenomas and in 20.5{\%} of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.",
author = "Tichomirowa, {Maria A.} and Anne Barlier and Daly, {Adrian F.} and Jaffrain-Rea, {Marie Lise} and Cristina Ronchi and Maria Yaneva and Urban, {Jonathan D.} and Patrick Petrossians and Atanaska Elenkova and Antoine Tabarin and Rachel Desailloud and Dominique Maiter and Thomas Sch{\"u}rmeyer and Renato Cozzi and Marily Theodoropoulou and Caroline Sievers and Ignacio Bernabeu and Naves, {Luciana A.} and Olivier Chabre and Monta{\~n}ana, {Carmen Fajardo} and Vaclav Hana and Georges Halaby and Brigitte Delemer and {Labarta Aizp{\'u}n}, {Jos{\'e} Ignacio} and Emmanuel Sonnet and {Ferrandez Long{\'a}s}, {\'A}ngel and Hagelstein, {Marie Th{\'e}r{\`e}se} and Philippe Caron and Stalla, {G{\"u}nter K.} and Vincent Bours and Sabina Zacharieva and Anna Spada and Thierry Brue and Albert Beckers",
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TY - JOUR

T1 - High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas

AU - Tichomirowa, Maria A.

AU - Barlier, Anne

AU - Daly, Adrian F.

AU - Jaffrain-Rea, Marie Lise

AU - Ronchi, Cristina

AU - Yaneva, Maria

AU - Urban, Jonathan D.

AU - Petrossians, Patrick

AU - Elenkova, Atanaska

AU - Tabarin, Antoine

AU - Desailloud, Rachel

AU - Maiter, Dominique

AU - Schürmeyer, Thomas

AU - Cozzi, Renato

AU - Theodoropoulou, Marily

AU - Sievers, Caroline

AU - Bernabeu, Ignacio

AU - Naves, Luciana A.

AU - Chabre, Olivier

AU - Montañana, Carmen Fajardo

AU - Hana, Vaclav

AU - Halaby, Georges

AU - Delemer, Brigitte

AU - Labarta Aizpún, José Ignacio

AU - Sonnet, Emmanuel

AU - Ferrandez Longás, Ángel

AU - Hagelstein, Marie Thérèse

AU - Caron, Philippe

AU - Stalla, Günter K.

AU - Bours, Vincent

AU - Zacharieva, Sabina

AU - Spada, Anna

AU - Brue, Thierry

AU - Beckers, Albert

PY - 2011/10

Y1 - 2011/10

N2 - Background: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. Methods: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. Results: Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. Conclusion: Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

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