PRKACA somatic mutations are rare findings in aldosterone-producing adenomas

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PRKACA somatic mutations are rare findings in aldosterone-producing adenomas. / Rhayem, Yara; Perez-Rivas, Luis G.; Dietz, Anna; Bathon, Kerstin; Gebhard, Christian; Riester, Anna; Mauracher, Brigitte; Gomez-Sanchez, Celso; Eisenhofer, Graeme; Schwarzmayr, Thomas; Calebiro, Davide; Strom, Tim M.; Reincke, Martin; Beuschlein, Felix.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 8, 01.08.2016, p. 3010-3017.

Research output: Contribution to journalArticle

Harvard

Rhayem, Y, Perez-Rivas, LG, Dietz, A, Bathon, K, Gebhard, C, Riester, A, Mauracher, B, Gomez-Sanchez, C, Eisenhofer, G, Schwarzmayr, T, Calebiro, D, Strom, TM, Reincke, M & Beuschlein, F 2016, 'PRKACA somatic mutations are rare findings in aldosterone-producing adenomas', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 8, pp. 3010-3017. https://doi.org/10.1210/jc.2016-1700

APA

Rhayem, Y., Perez-Rivas, L. G., Dietz, A., Bathon, K., Gebhard, C., Riester, A., Mauracher, B., Gomez-Sanchez, C., Eisenhofer, G., Schwarzmayr, T., Calebiro, D., Strom, T. M., Reincke, M., & Beuschlein, F. (2016). PRKACA somatic mutations are rare findings in aldosterone-producing adenomas. Journal of Clinical Endocrinology and Metabolism, 101(8), 3010-3017. https://doi.org/10.1210/jc.2016-1700

Vancouver

Author

Rhayem, Yara ; Perez-Rivas, Luis G. ; Dietz, Anna ; Bathon, Kerstin ; Gebhard, Christian ; Riester, Anna ; Mauracher, Brigitte ; Gomez-Sanchez, Celso ; Eisenhofer, Graeme ; Schwarzmayr, Thomas ; Calebiro, Davide ; Strom, Tim M. ; Reincke, Martin ; Beuschlein, Felix. / PRKACA somatic mutations are rare findings in aldosterone-producing adenomas. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 8. pp. 3010-3017.

Bibtex

@article{5e9c7c4924e749efbaccaa65c77300e7,
title = "PRKACA somatic mutations are rare findings in aldosterone-producing adenomas",
abstract = "Context: Somatic mutations have been found causative for endocrine autonomy in aldosteroneproducing adenomas (APAs). Whereas mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas, the presence of PRKACA variants in APAs is unknown, especially in those that display cosecretion of cortisol. Objective: The objective of the study was to investigate PRKACA somatic variants identified in APA cases. Design: Identification ofPRKACAsomatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues. Setting and Patients: APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for primary aldosteronism between 2005 and 2015 at a single institution. Results: PRKACA somatic mutations were identified in twoAPAcases (1.6%). OneAPAcarried a newly identified p.His88Asp variant,whereasinasecondcase,ap.Leu206Argmutationwasfound, previously described only in cortisol-producing adenomas with overt Cushing's syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. Although CYP11B2 was strongly expressed in the p.His88Asp-mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndromewaspresent only in the patient with the p.Leu206Arg mutation. After adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized serum potassium levels. Conclusions: We describe for the first time PRKACA mutations as rare findings associated with unilateral primary aldosteronism. As cortisol cosecretion occurs in a subgroup of APAs, other molecular mechanisms are likely to exist.",
author = "Yara Rhayem and Perez-Rivas, {Luis G.} and Anna Dietz and Kerstin Bathon and Christian Gebhard and Anna Riester and Brigitte Mauracher and Celso Gomez-Sanchez and Graeme Eisenhofer and Thomas Schwarzmayr and Davide Calebiro and Strom, {Tim M.} and Martin Reincke and Felix Beuschlein",
year = "2016",
month = aug,
day = "1",
doi = "10.1210/jc.2016-1700",
language = "English",
volume = "101",
pages = "3010--3017",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Endocrine Society",
number = "8",

}

RIS

TY - JOUR

T1 - PRKACA somatic mutations are rare findings in aldosterone-producing adenomas

AU - Rhayem, Yara

AU - Perez-Rivas, Luis G.

AU - Dietz, Anna

AU - Bathon, Kerstin

AU - Gebhard, Christian

AU - Riester, Anna

AU - Mauracher, Brigitte

AU - Gomez-Sanchez, Celso

AU - Eisenhofer, Graeme

AU - Schwarzmayr, Thomas

AU - Calebiro, Davide

AU - Strom, Tim M.

AU - Reincke, Martin

AU - Beuschlein, Felix

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Context: Somatic mutations have been found causative for endocrine autonomy in aldosteroneproducing adenomas (APAs). Whereas mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas, the presence of PRKACA variants in APAs is unknown, especially in those that display cosecretion of cortisol. Objective: The objective of the study was to investigate PRKACA somatic variants identified in APA cases. Design: Identification ofPRKACAsomatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues. Setting and Patients: APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for primary aldosteronism between 2005 and 2015 at a single institution. Results: PRKACA somatic mutations were identified in twoAPAcases (1.6%). OneAPAcarried a newly identified p.His88Asp variant,whereasinasecondcase,ap.Leu206Argmutationwasfound, previously described only in cortisol-producing adenomas with overt Cushing's syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. Although CYP11B2 was strongly expressed in the p.His88Asp-mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndromewaspresent only in the patient with the p.Leu206Arg mutation. After adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized serum potassium levels. Conclusions: We describe for the first time PRKACA mutations as rare findings associated with unilateral primary aldosteronism. As cortisol cosecretion occurs in a subgroup of APAs, other molecular mechanisms are likely to exist.

AB - Context: Somatic mutations have been found causative for endocrine autonomy in aldosteroneproducing adenomas (APAs). Whereas mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas, the presence of PRKACA variants in APAs is unknown, especially in those that display cosecretion of cortisol. Objective: The objective of the study was to investigate PRKACA somatic variants identified in APA cases. Design: Identification ofPRKACAsomatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues. Setting and Patients: APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for primary aldosteronism between 2005 and 2015 at a single institution. Results: PRKACA somatic mutations were identified in twoAPAcases (1.6%). OneAPAcarried a newly identified p.His88Asp variant,whereasinasecondcase,ap.Leu206Argmutationwasfound, previously described only in cortisol-producing adenomas with overt Cushing's syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. Although CYP11B2 was strongly expressed in the p.His88Asp-mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndromewaspresent only in the patient with the p.Leu206Arg mutation. After adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized serum potassium levels. Conclusions: We describe for the first time PRKACA mutations as rare findings associated with unilateral primary aldosteronism. As cortisol cosecretion occurs in a subgroup of APAs, other molecular mechanisms are likely to exist.

UR - http://www.scopus.com/inward/record.url?scp=84984705769&partnerID=8YFLogxK

U2 - 10.1210/jc.2016-1700

DO - 10.1210/jc.2016-1700

M3 - Article

AN - SCOPUS:84984705769

VL - 101

SP - 3010

EP - 3017

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 8

ER -