Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

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Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas. / Ronchi, Cristina L.; Peverelli, Erika; Herterich, Sabine; Weigand, Isabel; Mantovani, Giovanna; Schwarzmayr, Thomas; Sbiera, Silviu; Allolio, Bruno; Honegger, Jurgen; Appenzeller, Silke; Lania, Andrea G.; Reincke, Martin; Calebiro, Davide; Spada, Anna; Buchfelder, Michael; Flitsch, Joerg; Strom, Tim M.; Fassnacht, Martin.

In: European Journal of Endocrinology , Vol. 174, No. 3, 01.03.2016, p. 363-372.

Research output: Contribution to journalArticlepeer-review

Harvard

Ronchi, CL, Peverelli, E, Herterich, S, Weigand, I, Mantovani, G, Schwarzmayr, T, Sbiera, S, Allolio, B, Honegger, J, Appenzeller, S, Lania, AG, Reincke, M, Calebiro, D, Spada, A, Buchfelder, M, Flitsch, J, Strom, TM & Fassnacht, M 2016, 'Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas', European Journal of Endocrinology , vol. 174, no. 3, pp. 363-372. https://doi.org/10.1530/EJE-15-1064

APA

Ronchi, C. L., Peverelli, E., Herterich, S., Weigand, I., Mantovani, G., Schwarzmayr, T., Sbiera, S., Allolio, B., Honegger, J., Appenzeller, S., Lania, A. G., Reincke, M., Calebiro, D., Spada, A., Buchfelder, M., Flitsch, J., Strom, T. M., & Fassnacht, M. (2016). Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas. European Journal of Endocrinology , 174(3), 363-372. https://doi.org/10.1530/EJE-15-1064

Vancouver

Ronchi CL, Peverelli E, Herterich S, Weigand I, Mantovani G, Schwarzmayr T et al. Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas. European Journal of Endocrinology . 2016 Mar 1;174(3):363-372. https://doi.org/10.1530/EJE-15-1064

Author

Ronchi, Cristina L. ; Peverelli, Erika ; Herterich, Sabine ; Weigand, Isabel ; Mantovani, Giovanna ; Schwarzmayr, Thomas ; Sbiera, Silviu ; Allolio, Bruno ; Honegger, Jurgen ; Appenzeller, Silke ; Lania, Andrea G. ; Reincke, Martin ; Calebiro, Davide ; Spada, Anna ; Buchfelder, Michael ; Flitsch, Joerg ; Strom, Tim M. ; Fassnacht, Martin. / Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas. In: European Journal of Endocrinology . 2016 ; Vol. 174, No. 3. pp. 363-372.

Bibtex

@article{5e9bddd8722a445d8a4524beedf1bcc9,
title = "Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas",
abstract = "Context: Alterations in the cAMP signaling 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 (nZ31) and next-generation exome sequencing (nZ36). Results: By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8. Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1-13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight 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 significant correlation between genetic alterations and the clinical data was observed. Conclusion: 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 signaling might be involved in the pathogenesis of these tumors.",
author = "Ronchi, {Cristina L.} and Erika Peverelli and Sabine Herterich and Isabel Weigand and Giovanna Mantovani and Thomas Schwarzmayr and Silviu Sbiera and Bruno Allolio and Jurgen Honegger and Silke Appenzeller and Lania, {Andrea G.} and Martin Reincke and Davide Calebiro and Anna Spada and Michael Buchfelder and Joerg Flitsch and Strom, {Tim M.} and Martin Fassnacht",
year = "2016",
month = mar,
day = "1",
doi = "10.1530/EJE-15-1064",
language = "English",
volume = "174",
pages = "363--372",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica",
number = "3",

}

RIS

TY - JOUR

T1 - Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

AU - Ronchi, Cristina L.

AU - Peverelli, Erika

AU - Herterich, Sabine

AU - Weigand, Isabel

AU - Mantovani, Giovanna

AU - Schwarzmayr, Thomas

AU - Sbiera, Silviu

AU - Allolio, Bruno

AU - Honegger, Jurgen

AU - Appenzeller, Silke

AU - Lania, Andrea G.

AU - Reincke, Martin

AU - Calebiro, Davide

AU - Spada, Anna

AU - Buchfelder, Michael

AU - Flitsch, Joerg

AU - Strom, Tim M.

AU - Fassnacht, Martin

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Context: Alterations in the cAMP signaling 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 (nZ31) and next-generation exome sequencing (nZ36). Results: By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8. Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1-13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight 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 significant correlation between genetic alterations and the clinical data was observed. Conclusion: 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 signaling might be involved in the pathogenesis of these tumors.

AB - Context: Alterations in the cAMP signaling 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 (nZ31) and next-generation exome sequencing (nZ36). Results: By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8. Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1-13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight 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 significant correlation between genetic alterations and the clinical data was observed. Conclusion: 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 signaling might be involved in the pathogenesis of these tumors.

UR - http://www.scopus.com/inward/record.url?scp=84958245883&partnerID=8YFLogxK

U2 - 10.1530/EJE-15-1064

DO - 10.1530/EJE-15-1064

M3 - Article

C2 - 26701869

AN - SCOPUS:84958245883

VL - 174

SP - 363

EP - 372

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 3

ER -