Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis.
Thomas Cuny
(1, 2)
,
Morgane Pertuit
(3, 4)
,
Mona Sahnoun-Fathallah
(5)
,
Adrian Daly
(6)
,
Gianluca Occhi
(7)
,
Marie Françoise Odou
(8)
,
Antoine Tabarin
(9)
,
Marie Laure Nunes
(9)
,
Brigitte Delemer
(10)
,
Vincent Rohmer
(11)
,
Rachel Desailloud
(12)
,
Véronique Kerlan
(13, 14)
,
Olivier Chabre
(15, 16)
,
Jean-Louis Sadoul
(17)
,
Muriel Cogne
(18)
,
Philippe Caron
(19)
,
Christine Cortet-Rudelli
(20)
,
Anne Lienhardt-Roussie
(21)
,
Isabelle Raingeard
(22)
,
Anne-Marie Guedj
(23)
,
Thierry Brue
(5, 2)
,
Albert Beckers
(6)
,
Georges Weryha
(1)
,
Alain Enjalbert
(4, 2)
,
Anne A. Barlier
(4, 2)
1
Service d'Endocrinologie [CHRU Nancy]
2 CRN2M - Centre de recherche en neurobiologie - neurophysiologie de Marseille
3 ICN - Interactions cellulaires neuroendocriniennes
4 MARSEILLE - Biolo Moléculaire - Laboratoire de Biologie Moléculaire
5 Service d'endocrinologie, diabète et maladies métaboliques
6 LIEGE - Endocrino - Service d'Endocrinologie
7 PADOVA - Médecine - Département de Médecine
8 Institut de Biochimie et Biologie Moléculaire [CHRU Lille]
9 BORDEAUX - Endocrino - Service d'Endocrinologie
10 Service d'Endocrinologie - Diabète - Nutrition [Reims]
11 ANGERS - Endocrino - Service d'Endocrinologie
12 AMIENS - Endocrino - Service d'Endocrinologie
13 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
14 CHRU - Endocrino - Service d'Endocrinologie
15 BCI - Biologie du Cancer et de l'Infection
16 GRENOBLE - Endocrino - Service d'Endocrinologie
17 NICE - Endocrino - Service d'Endocrinologie
18 ST PIERRE LA REUNION - Endocrino - Service d'Endocrinologie
19 Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse]
20 LILLE - Endocrino - Service Endocrinologie, diabétologie, maladies métaboliques et nutrition
21 Service de Pédiatrie médicale [CHU Limoges]
22 MONTPELLIER - Endocrino - Service d'Endocrinologie
23 NIMES - Endocrino - Service d'Endocrinologie
2 CRN2M - Centre de recherche en neurobiologie - neurophysiologie de Marseille
3 ICN - Interactions cellulaires neuroendocriniennes
4 MARSEILLE - Biolo Moléculaire - Laboratoire de Biologie Moléculaire
5 Service d'endocrinologie, diabète et maladies métaboliques
6 LIEGE - Endocrino - Service d'Endocrinologie
7 PADOVA - Médecine - Département de Médecine
8 Institut de Biochimie et Biologie Moléculaire [CHRU Lille]
9 BORDEAUX - Endocrino - Service d'Endocrinologie
10 Service d'Endocrinologie - Diabète - Nutrition [Reims]
11 ANGERS - Endocrino - Service d'Endocrinologie
12 AMIENS - Endocrino - Service d'Endocrinologie
13 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
14 CHRU - Endocrino - Service d'Endocrinologie
15 BCI - Biologie du Cancer et de l'Infection
16 GRENOBLE - Endocrino - Service d'Endocrinologie
17 NICE - Endocrino - Service d'Endocrinologie
18 ST PIERRE LA REUNION - Endocrino - Service d'Endocrinologie
19 Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse]
20 LILLE - Endocrino - Service Endocrinologie, diabétologie, maladies métaboliques et nutrition
21 Service de Pédiatrie médicale [CHU Limoges]
22 MONTPELLIER - Endocrino - Service d'Endocrinologie
23 NIMES - Endocrino - Service d'Endocrinologie
Thomas Cuny
- Function : Author
- PersonId : 19746
- IdHAL : thomas-cuny
- ORCID : 0000-0002-8440-0030
- IdRef : 166087718
Rachel Desailloud
- Function : Author
- PersonId : 767326
- IdHAL : desailra
- ORCID : 0000-0001-9976-7938
- IdRef : 078643422
Philippe Caron
- Function : Author
- PersonId : 1321942
- ORCID : 0000-0001-5391-7582
- IdRef : 056739737
Anne Lienhardt-Roussie
- Function : Author
- PersonId : 931417
Thierry Brue
- Function : Author
- PersonId : 16653
- IdHAL : thierry-brue
- ORCID : 0000-0001-8482-6691
- IdRef : 058613439
Anne A. Barlier
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 16684
- IdHAL : anne-barlier
- ORCID : 0000-0002-3740-6173
- IdRef : 143313339
Connectez-vous pour contacter l'auteur
Abstract
CONTEXT: Germline mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) have been identified in young patients (age ≤30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of multiple endocrine neoplasia type 1 (MEN1) mutations in such a population. OBJECTIVE: We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age ≤30 years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions. DESIGN: The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions. PATIENTS AND SETTINGS: One hundred and seventy-four patients from endocrinology departments of 15 French University Hospital Centers were eligible for this study. RESULTS: Twenty-one out of 174 (12%) patients had AIP (n=15, 8.6%) or MEN1 (n=6, 3.4%) mutations. In pediatric patients (age ≤18 years old), AIP/MEN1 mutation frequency reached nearly 22% (n=10/46). AIPmut and MEN1mut were identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients respectively; they each accounted for 4/74 (5.4%) prolactinoma (PRL) patients with mutations. Half of those patients (n=3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the eight corticotroph adenomas or the single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients. CONCLUSION: Mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly PRL, and together with AIP, we suggest genetic analysis of MEN1 in such a population.