Article (Scientific journals)
Screening for GPR101 defects in pediatric pituitary corticotropinomas.
Trivellin, Giampaolo; Correa, Ricardo R.; Batsis, Maria et al.
2016In Endocrine-Related Cancer, 23 (5), p. 357-365
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Abstract :
[en] Cushing disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. We investigated the orphan G protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas. We performed GPR101 sequencing, expression analyses by RT-qPCR and immunostaining, and functional studies (cell proliferation, pituitary hormones secretion, and cAMP measurement) in a series of patients with sporadic CD secondary to ACTH-secreting adenomas in whom we had peripheral and tumor DNA (N=36). No increased GPR101 expression was observed in tumors compared to normal pituitary (NP) tissues, nor did we find a correlation between GPR101 and ACTH expression levels. Sequence analysis revealed a very rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD. Overexpression of the p.G31S variant did not lead to increased growth and proliferation, although modest effects on cAMP signaling were seen. GPR101 is not overexpressed in ACTH-secreting tumors compared to NPs. A rare germline GPR101 variant was found in one patient with CD but in vitro studies did not support a consistent pathogenic effect. GPR101 is unlikely to be involved in the pathogenesis of CD.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Trivellin, Giampaolo 
Correa, Ricardo R. 
Batsis, Maria
Faucz, Fabio R.
Chittiboina, Prashant
Bjelobaba, Ivana
Larco, Darwin O.
Quezado, Martha
Daly, Adrian  ;  Université de Liège > Département des sciences cliniques > Endocrinologie
Stojilkovic, Stanko S.
Wu, T. John
Beckers, Albert ;  Université de Liège > Département des sciences cliniques > Endocrinologie
Lodish, Maya
Stratakis, Constantine A.
More authors (4 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Screening for GPR101 defects in pediatric pituitary corticotropinomas.
Publication date :
2016
Journal title :
Endocrine-Related Cancer
ISSN :
1351-0088
eISSN :
1479-6821
Publisher :
Society for Endocrinology, United Kingdom
Volume :
23
Issue :
5
Pages :
357-365
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 March 2016

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