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Ronchi, C.L.* ; Peverelli, E.* ; Herterich, S.* ; Weigand, I.* ; Mantovani, G.* ; Schwarzmayr, T. ; Sbiera, S.* ; Allolio, B.* ; Honegger, J.* ; Appenzeller, S.* ; Lania, A.* ; Reincke, M.* ; Calebiro, D.* ; Spada, A.* ; Buchfelder, M.* ; Flitsch, J.* ; Strom, T.M.* ; Fassnacht, M.*

Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas.

Eur. J. Endocrinol. 174, 363-372 (2016)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
CONTEXT: Alterations in the cAMP signalling pathway are common in hormonally-active endocrine tumors. Somatic mutations at GNAS are causative in 30-40% of GH-secreting adenomas. Recently, mutations affecting the USP8 and PRKACA gene have been reported in ACTH-secreting pituitary adenomas and cortisol-secreting adrenocortical adenomas, respectively. However, the pathogenesis of many GH-secreting adenomas remains unclear. AIM: Comprehensive genetic characterization of sporadic GH-secreting adenomas and identification of new driver mutations. DESIGN: Screening for somatic mutations was performed in 67 GH-secreting adenomas by targeted sequencing for GNAS, PRKACA, and USP8 mutations (n=31) and next-generation exome-sequencing (n=36). RESULTS: By targeted sequencing known activating mutations in GNAS were detected in 5 cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8. Whole exome sequencing identified 134 protein-altering somatic mutations in 31/36 tumors with a median of 3 mutations per sample (range: 1-13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, 7 genes involved in cAMP signalling pathway were affected in 14 of 36 samples and 8 samples harbored variants in genes involved in the calcium signaling or metabolism. At the enrichment analysis, several altered genes resulted to be associated with developmental processes. No correlation between genetic alterations and the clinical data was observed. CONCLUSIONS: This study provides a comprehensive analysis of somatic mutations in a large series of GH-secreting adenomas. No novel recurrent genetic alterations have been observed, but the data suggest that beside cAMP pathway calcium signalling might be involved in the pathogenesis of these tumors.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Protein-kinase-a; Adrenal Cushings-syndrome; Epidermal-growth-factor; Pka Catalytic Subunit; Somatotroph Adenomas; Regulatory Subunit; Adrenocortical Hyperplasia; Acromegalic Patients; Activating Mutation; Sequence-analysis
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 0804-4643
e-ISSN 1479-683X
Zeitschrift European Journal of Endocrinology
Quellenangaben Band: 174, Heft: 3, Seiten: 363-372 Artikelnummer: , Supplement: ,
Verlag BioScientifica
Verlagsort Bristol
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
DOI 10.1530/EJE-15-1064
WOS ID WOS:000370876800017
Scopus ID 84958245883
PubMed ID 26701869
Erfassungsdatum 2016-01-08
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