Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Adolescent Adrenal Cortex Neoplasms / genetics Adrenocortical Adenoma / genetics Adult Aldosterone / biosynthesis Female GTP-Binding Protein alpha Subunits / genetics GTP-Binding Protein alpha Subunits, Gq-G11 / genetics Humans Hyperaldosteronism / pathology Male Menopause / metabolism Middle Aged Pregnancy Puberty / metabolism beta Catenin / genetics

Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
09 2021
Historique:
received: 23 07 2020
accepted: 29 06 2021
pubmed: 14 8 2021
medline: 15 10 2021
entrez: 13 8 2021
Statut: ppublish

Résumé

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.

Identifiants

DOI: 10.1038/s41588-021-00906-y PMID: 34385710 PMC: PMC9082578
pubmed: 34385710
doi: 10.1038/s41588-021-00906-y
pii: 10.1038/s41588-021-00906-y
pmc: PMC9082578
mid: NIHMS1796697
doi:

Substances chimiques

CTNNB1 protein, human 0
GNA11 protein, human 0
GNAQ protein, human 0
GTP-Binding Protein alpha Subunits 0
beta Catenin 0
Aldosterone 4964P6T9RB
GTP-Binding Protein alpha Subunits, Gq-G11 EC 3.6.5.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1360-1372

Subventions

Organisme : British Heart Foundation
ID : SP/08/002/24118
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/11/35/28871
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K501050/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL144847
Pays : United States
Organisme : British Heart Foundation
ID : PG/16/40/32137
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/50/34566
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/07/085/23349
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S006869/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106995/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K020455/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801265
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/75/31134
Pays : United Kingdom
Organisme : BLRD VA
ID : I01 BX004681
Pays : United States
Organisme : British Heart Foundation
ID : FS/14/12/30540
Pays : United Kingdom

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

Références

Choi, M. et al. K
pubmed: 21311022 pmcid: 3371087 doi: 10.1126/science.1198785
Beuschlein, F. et al. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat. Genet. 45, 440–444 (2013).
pubmed: 23416519 doi: 10.1038/ng.2550
Scholl, U. I. et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat. Genet. 45, 1050–1054 (2013).
pubmed: 23913001 pmcid: 3876926 doi: 10.1038/ng.2695
Azizan, E. A. et al. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat. Genet. 45, 1055–1060 (2013).
pubmed: 23913004 doi: 10.1038/ng.2716
Azizan, E. A. et al. Microarray, qPCR and KCNJ5 sequencing of aldosterone-producing adenomas reveal differences in genotype and phenotype between zona glomerulosa- and zona fasciculata-like tumors. J. Clin. Endocrinol. Metab. 97, E819–E829 (2012).
pubmed: 22442279 doi: 10.1210/jc.2011-2965
Monticone, S. et al. Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas. Mol. Cell Endocrinol. 411, 146–154 (2015).
pubmed: 25958045 pmcid: 4474471 doi: 10.1016/j.mce.2015.04.022
Akerstrom, T. et al. Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas. Endocr. Relat. Cancer 22, 735–744 (2015).
pubmed: 26285814 doi: 10.1530/ERC-15-0321
De Sousa, K. et al. Genetic, cellular, and molecular heterogeneity in adrenals with aldosterone-producing adenoma. Hypertension 75, 1034–1044 (2020).
pubmed: 32114847 doi: 10.1161/HYPERTENSIONAHA.119.14177
Nanba, K. et al. Targeted molecular characterization of aldosterone-producing adenomas in White Americans. J. Clin. Endocrinol. Metab. 103, 3869–3876 (2018).
pubmed: 30085035 pmcid: 6179168 doi: 10.1210/jc.2018-01004
Wu, V. C. et al. The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes. Sci. Rep. 7, 39121 (2017).
pubmed: 28102204 pmcid: 5244399 doi: 10.1038/srep39121
Nishimoto, K. et al. Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands. Proc. Natl Acad. Sci. USA 112, E4591–E4599 (2015).
pubmed: 26240369 pmcid: 4547250 doi: 10.1073/pnas.1505529112
Williams, T. A. et al. Visinin-like 1 is upregulated in aldosterone-producing adenomas with KCNJ5 mutations and protects from calcium-induced apoptosis. Hypertension 59, 833–839 (2012).
pubmed: 22331379 doi: 10.1161/HYPERTENSIONAHA.111.188532
Akerstrom, T. et al. Activating mutations in CTNNB1 in aldosterone producing adenomas. Sci. Rep. 6, 19546 (2016).
pubmed: 26815163 pmcid: 4728393 doi: 10.1038/srep19546
Tadjine, M., Lampron, A., Ouadi, L. & Bourdeau, I. Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas. Clin. Endocrinol. (Oxf.) 68, 264–270 (2008).
Omata, K. et al. Cellular and genetic causes of idiopathic hyperaldosteronism. Hypertension 72, 874–880 (2018).
pubmed: 30354720 doi: 10.1161/HYPERTENSIONAHA.118.11086
Teo, A. E. et al. Pregnancy, primary aldosteronism, and adrenal CTNNB1 mutations. N. Engl. J. Med. 373, 1429–1436 (2015).
pubmed: 26397949 pmcid: 4612399 doi: 10.1056/NEJMoa1504869
Kalinec, G., Nazarali, A. J., Hermouet, S., Xu, N. & Gutkind, J. S. Mutated alpha subunit of the Gq protein induces malignant transformation in NIH 3T3 cells. Mol. Cell Biol. 12, 4687–4693 (1992).
pubmed: 1328859 pmcid: 360395
Gutowski, S. et al. Antibodies to the alpha q subfamily of guanine nucleotide-binding regulatory protein alpha subunits attenuate activation of phosphatidylinositol 4,5-bisphosphate hydrolysis by hormones. J. Biol. Chem. 266, 20519–20524 (1991).
pubmed: 1657928 doi: 10.1016/S0021-9258(18)54955-3
Backman, S. et al. RNA sequencing provides novel insights into the transcriptome of aldosterone producing adenomas. Sci. Rep. 9, 6269 (2019).
pubmed: 31000732 pmcid: 6472367 doi: 10.1038/s41598-019-41525-2
Wiese, M. et al. The beta-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner. Oncotarget 8, 27300–27313 (2017).
pubmed: 28460484 pmcid: 5432336 doi: 10.18632/oncotarget.15934
Zhou, L. et al. Multiple genes of the renin-angiotensin system are novel targets of Wnt/beta-catenin signaling. J. Am. Soc. Nephrol. 26, 107–120 (2015).
pubmed: 25012166 doi: 10.1681/ASN.2014010085
Doghman, M., Cazareth, J. & Lalli, E. The T cell factor/beta-catenin antagonist PKF115-584 inhibits proliferation of adrenocortical carcinoma cells. J. Clin. Endocrinol. Metab. 93, 3222–3225 (2008).
pubmed: 18544621 doi: 10.1210/jc.2008-0247
Zhou, T. et al. CTNNB1 knockdown inhibits cell proliferation and aldosterone secretion through inhibiting Wnt/beta-catenin signaling in H295R cells. Technol. Cancer Res. Treat. 19, 1533033820979685 (2020).
pubmed: 33287648 pmcid: 7727057
Jeppesen, J. V. et al. LH-receptor gene expression in human granulosa and cumulus cells from antral and preovulatory follicles. J. Clin. Endocrinol. Metab. 97, E1524–E1531 (2012).
pubmed: 22659248 pmcid: 3410279 doi: 10.1210/jc.2012-1427
Breen, S. M. et al. Ovulation involves the luteinizing hormone-dependent activation of G(q/11) in granulosa cells. Mol. Endocrinol. 27, 1483–1491 (2013).
pubmed: 23836924 pmcid: 3753423 doi: 10.1210/me.2013-1130
Gazdar, A. F. et al. Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis. Cancer Res. 50, 5488–5496 (1990).
pubmed: 2386954
Tissier, F. et al. Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Res. 65, 7622–7627 (2005).
pubmed: 16140927 doi: 10.1158/0008-5472.CAN-05-0593
Boulkroun, S. et al. Aldosterone-producing adenoma formation in the adrenal cortex involves expression of stem/progenitor cell markers. Endocrinology 152, 4753–4763 (2011).
pubmed: 21971159 doi: 10.1210/en.2011-1205
Shaikh, L. H. et al. LGR5 activates noncanonical Wnt signaling and inhibits aldosterone production in the human adrenal. J. Clin. Endocrinol. Metab. 100, E836–E844 (2015).
pubmed: 25915569 pmcid: 4454794 doi: 10.1210/jc.2015-1734
Zhou, J. et al. Transcriptome pathway analysis of pathological and physiological aldosterone-producing human tissues. Hypertension 68, 1424–1431 (2016).
pubmed: 27777363 doi: 10.1161/HYPERTENSIONAHA.116.08033
Taylor, M. J. et al. Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation. J. Clin. Invest. 130, 83–93 (2020).
pubmed: 31738186 doi: 10.1172/JCI127429
Leng, S. et al. beta-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis. Nat. Commun. 11, 1680 (2020).
pubmed: 32245949 pmcid: 7125176 doi: 10.1038/s41467-020-15332-7
Schwindinger, W. F., Francomano, C. A. & Levine, M. A. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune–Albright syndrome. Proc. Natl Acad. Sci. USA 89, 5152–5156 (1992).
pubmed: 1594625 pmcid: 49247 doi: 10.1073/pnas.89.11.5152
Weinstein, L. S. et al. Activating mutations of the stimulatory G protein in the McCune–Albright syndrome. N. Engl. J. Med. 325, 1688–1695 (1991).
pubmed: 1944469 doi: 10.1056/NEJM199112123252403
Idowu, B. D. et al. A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone. Histopathology 50, 691–704 (2007).
pubmed: 17493233 doi: 10.1111/j.1365-2559.2007.02676.x
Vasilev, V. et al. McCune–Albright syndrome: a detailed pathological and genetic analysis of disease effects in an adult patient. J. Clin. Endocrinol. Metab. 99, E2029–E2038 (2014).
pubmed: 25062453 doi: 10.1210/jc.2014-1291
Rey, R. A. et al. Unexpected mosaicism of R201H-GNAS1 mutant-bearing cells in the testes underlie macro-orchidism without sexual precocity in McCune–Albright syndrome. Hum. Mol. Genet. 15, 3538–3543 (2006).
pubmed: 17101633 doi: 10.1093/hmg/ddl430
Wu, D. Q., Lee, C. H., Rhee, S. G. & Simon, M. I. Activation of phospholipase C by the alpha subunits of the Gq and G11 proteins in transfected Cos-7 cells. J. Biol. Chem. 267, 1811–1817 (1992).
pubmed: 1309799 doi: 10.1016/S0021-9258(18)46018-8
Ayturk, U. M. et al. Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma. Am. J. Hum. Genet. 98, 789–795 (2016).
pubmed: 27058448 pmcid: 4833432 doi: 10.1016/j.ajhg.2016.03.009
Van Raamsdonk, C. D. et al. Mutations in GNA11 in uveal melanoma. N. Engl. J. Med. 363, 2191–2199 (2010).
pubmed: 21083380 pmcid: 3107972 doi: 10.1056/NEJMoa1000584
Shirley, M. D. et al. Sturge–Weber syndrome and port-wine stains caused by somatic mutation in Gnaq. N. Engl. J. Med. 368, 1971–1979 (2013).
pubmed: 23656586 pmcid: 3749068 doi: 10.1056/NEJMoa1213507
Thomas, A. C. et al. Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis. J. Invest. Dermatol. 136, 770–778 (2016).
pubmed: 26778290 pmcid: 4803466 doi: 10.1016/j.jid.2015.11.027
Simon, D. P. & Hammer, G. D. Adrenocortical stem and progenitor cells: implications for adrenocortical carcinoma. Mol. Cell Endocrinol. 351, 2–11 (2012).
pubmed: 22266195 pmcid: 3288146 doi: 10.1016/j.mce.2011.12.006
Berthon, A. et al. WNT/beta-catenin signalling is activated in aldosterone-producing adenomas and controls aldosterone production. Hum. Mol. Genet. 23, 889–905 (2014).
pubmed: 24087794 doi: 10.1093/hmg/ddt484
Lerario, A. M., Moraitis, A. & Hammer, G. D. Genetics and epigenetics of adrenocortical tumors. Mol. Cell Endocrinol. 386, 67–84 (2014).
pubmed: 24220673 doi: 10.1016/j.mce.2013.10.028
Wang, J. J., Peng, K. Y., Wu, V. C., Tseng, F. Y. & Wu, K. D. CTNNB1 mutation in aldosterone producing adenoma. Endocrinol. Metab. (Seoul) 32, 332–338 (2017).
doi: 10.3803/EnM.2017.32.3.332
Assie, G. et al. Integrated genomic characterization of adrenocortical carcinoma. Nat. Genet. 46, 607–612 (2014).
pubmed: 24747642 doi: 10.1038/ng.2953
Jakobsen, J. N., Santoni-Rugiu, E., Grauslund, M., Melchior, L. & Sorensen, J. B. Concomitant driver mutations in advanced EGFR-mutated non-small-cell lung cancer and their impact on erlotinib treatment. Oncotarget 9, 26195–26208 (2018).
pubmed: 29899852 pmcid: 5995236 doi: 10.18632/oncotarget.25490
Gainor, J. F. et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin. Cancer Res. 19, 4273–4281 (2013).
pubmed: 23729361 doi: 10.1158/1078-0432.CCR-13-0318
Nanba, K. et al. Genetic characteristics of aldosterone-producing adenomas in Blacks. Hypertension 73, 885–892 (2019).
pubmed: 30739536 doi: 10.1161/HYPERTENSIONAHA.118.12070
Pignatti, E. et al. Beta-catenin causes adrenal hyperplasia by blocking zonal transdifferentiation. Cell Rep. 31, 107524 (2020).
pubmed: 32320669 pmcid: 7281829 doi: 10.1016/j.celrep.2020.107524
Vouillarmet, J. et al. Aldosterone-producing adenoma with a somatic KCNJ5 mutation revealing APC-dependent familial adenomatous polyposis. J. Clin. Endocrinol. Metab. 101, 3874–3878 (2016).
pubmed: 27648962 doi: 10.1210/jc.2016-1874
Polak, P. et al. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 518, 360–364 (2015).
pubmed: 25693567 pmcid: 4405175 doi: 10.1038/nature14221
Yeh, I. et al. Combined activation of MAP kinase pathway and beta-catenin signaling cause deep penetrating nevi. Nat. Commun. 8, 644 (2017).
pubmed: 28935960 pmcid: 5608693 doi: 10.1038/s41467-017-00758-3
Piaggio, F. et al. Secondary somatic mutations in G-protein-related pathways and mutation signatures in uveal melanoma. Cancers (Basel) 11, 1688 (2019).
doi: 10.3390/cancers11111688
Chen, X. et al. The melanoma-linked ‘redhead’ MC1R influences dopaminergic neuron survival. Ann. Neurol. 81, 395–406 (2017).
pubmed: 28019657 pmcid: 6085083 doi: 10.1002/ana.24852
Cavlan, D., Storr, H. L., Berney, D., Evagora, C. & King, P. J. Adrenal pigmentation in PPNAD is a result of melanin deposition and associated with upregulation of the melanocortin 1 receptor. Endocr. Abstr. 38, 154 (2015).
Binder, J. X. et al. COMPARTMENTS: unification and visualization of protein subcellular localization evidence. Database (Oxf.) 2014, bau012 (2014).
doi: 10.1093/database/bau012
de Lau, W. et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476, 293–297 (2011).
pubmed: 21727895 doi: 10.1038/nature10337
Vidal, V. et al. The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3. Genes Dev. 30, 1389–1394 (2016).
pubmed: 27313319 pmcid: 4926862 doi: 10.1101/gad.277756.116
Yi, H., Wang, Y., Kavallaris, M. & Wang, J. Y. Lgr4-mediated potentiation of Wnt/β-catenin signaling promotes MLL leukemogenesis via an Rspo3/Wnt3a-Gnaq pathway in leukemic stem cells. Blood 122, 887 (2013).
doi: 10.1182/blood.V122.21.887.887
Carter, J. M. et al. CTNNB1 mutations and estrogen receptor expression in neuromuscular choristoma and its associated fibromatosis. Am. J. Surg. Pathol. 40, 1368–1374 (2016).
pubmed: 27259010 doi: 10.1097/PAS.0000000000000673
Crago, A. M. et al. Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis. Genes Chromosomes Cancer 54, 606–615 (2015).
pubmed: 26171757 pmcid: 4548882 doi: 10.1002/gcc.22272
Maria, A. G. et al. Mosaicism for KCNJ5 causing early-onset primary aldosteronism due to bilateral adrenocortical hyperplasia. Am. J. Hypertens. 33, 124–130 (2020).
pubmed: 31637427 doi: 10.1093/ajh/hpz172
Zhang, E. D. et al. Mutation spectrum in GNAQ and GNA11 in Chinese uveal melanoma. Precis. Clin. Med. 2, 213–220 (2019).
doi: 10.1093/pcmedi/pbz021 pubmed: 35693877 pmcid: 8985776
Gerstenblith, M. R., Goldstein, A. M., Fargnoli, M. C., Peris, K. & Landi, M. T. Comprehensive evaluation of allele frequency differences of MC1R variants across populations. Hum. Mutat. 28, 495–505 (2007).
pubmed: 17279550 doi: 10.1002/humu.20476
Eguchi, K. et al. An adverse pregnancy-associated outcome due to overlooked primary aldosteronism. Intern. Med. 53, 2499–2504 (2014).
pubmed: 25366010 doi: 10.2169/internalmedicine.53.2762
Saner-Amigh, K. et al. Elevated expression of luteinizing hormone receptor in aldosterone-producing adenomas. J. Clin. Endocrinol. Metab. 91, 1136–1142 (2006).
pubmed: 16332935 doi: 10.1210/jc.2005-1298
Gagnon, N. et al. Genetic characterization of GnRH/LH-responsive primary aldosteronism. J. Clin. Endocrinol. Metab. 103, 2926–2935 (2018).
pubmed: 29726953 doi: 10.1210/jc.2018-00087
Albiger, N. M. et al. A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion? Eur. J. Endocrinol. 164, 405–412 (2011).
pubmed: 21330483 doi: 10.1530/EJE-10-0879
Berthon, A., Drelon, C. & Val, P. Pregnancy, primary aldosteronism, and somatic CTNNB1 mutations. N. Engl. J. Med. 374, 1493–1494 (2016).
pubmed: 27074082
Murtha, T. D., Carling, T. & Scholl, U. I. Pregnancy, primary aldosteronism, and somatic CTNNB1 mutations. N. Engl. J. Med. 374, 1492–1493 (2016).
pubmed: 27074081 doi: 10.1056/NEJMc1514508
Burton, T. J. et al. Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn’s adenomas. J. Clin. Endocrinol. Metab. 97, 100–109 (2012).
pubmed: 22112805 doi: 10.1210/jc.2011-1537
Letavernier, E. et al. Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma. J. Hypertens. 26, 1816–1823 (2008).
pubmed: 18698217 doi: 10.1097/HJH.0b013e3283060f0c
Funder, J. W. et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 93, 3266–3281 (2008).
pubmed: 18552288 doi: 10.1210/jc.2008-0104
Fernandes-Rosa, F. L. et al. Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma. Hypertension 54, 354–361 (2014).
doi: 10.1161/HYPERTENSIONAHA.114.03419
Akerstrom, T. et al. Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter. PLoS ONE 7, e41926 (2012).
pubmed: 22848660 pmcid: 3407065 doi: 10.1371/journal.pone.0041926
Gomez-Sanchez, C. E. et al. Development of monoclonal antibodies against human CYP11B1 and CYP11B2. Mol. Cell Endocrinol. 383, 111–117 (2014).
pubmed: 24325867 doi: 10.1016/j.mce.2013.11.022
Bustin, S. A. Why the need for qPCR publication guidelines? The case for MIQE. Methods 50, 217–226 (2010).
pubmed: 20025972 doi: 10.1016/j.ymeth.2009.12.006

Auteurs

Junhua Zhou (J)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
ORCID: 0000-0002-8593-8393

Elena A B Azizan (EAB)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK. elena.azizan@ukm.edu.my.
Department of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia. elena.azizan@ukm.edu.my.
ORCID: 0000-0002-5549-4242

Claudia P Cabrera (CP)

NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Centre for Translational Bioinformatics, William Harvey Research Institute, Queen Mary University of London, London, UK.

Fabio L Fernandes-Rosa (FL)

Université de Paris, PARCC, Inserm, Paris, France.
ORCID: 0000-0002-0162-0792

Sheerazed Boulkroun (S)

Université de Paris, PARCC, Inserm, Paris, France.
ORCID: 0000-0002-8796-7534

Giulia Argentesi (G)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Emily Cottrell (E)

Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.
ORCID: 0000-0001-6773-6547

Laurence Amar (L)

Université de Paris, PARCC, Inserm, Paris, France.
Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Unité Hypertension Artérielle, Paris, France.

Xilin Wu (X)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Sam O'Toole (S)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
ORCID: 0000-0002-8943-8556

Emily Goodchild (E)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Alison Marker (A)

Department of Histopathology, Addenbrooke's Hospital, Cambridge, UK.

Russell Senanayake (R)

Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.

Sumedha Garg (S)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
ORCID: 0000-0002-4375-8968

Tobias Åkerström (T)

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Samuel Backman (S)

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
ORCID: 0000-0002-4208-9395

Suzanne Jordan (S)

Cellular Pathology Department, Royal London Hospital, London, UK.

Satyamaanasa Polubothu (S)

Genetics and Genomic Medicine, University College London Great Ormond Street Institute of Child Health, London, UK.

Daniel M Berney (DM)

Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.

Anna Gluck (A)

Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Kate E Lines (KE)

Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
ORCID: 0000-0002-0764-8681

Rajesh V Thakker (RV)

Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
ORCID: 0000-0002-1438-3220

Antoinette Tuthill (A)

Department of Endocrinology and Diabetes, Cork University Hospital, Cork, Ireland.
ORCID: 0000-0002-1460-517X

Caroline Joyce (C)

Clinical Biochemistry, Cork University Hospital, Cork, Ireland.

Juan Pablo Kaski (JP)

Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital and University College London Institute of Cardiovascular Science, London, UK.
ORCID: 0000-0002-0014-9927

Fiona E Karet Frankl (FE)

Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

Lou A Metherell (LA)

Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.
ORCID: 0000-0002-0530-3524

Ada E D Teo (AED)

Dept of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
ORCID: 0000-0002-8832-0409

Mark Gurnell (M)

Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
ORCID: 0000-0001-5745-6832

Laila Parvanta (L)

Department of Surgery, St Bartholomew's Hospital, London, UK.

William M Drake (WM)

Department of Endocrinology, St Bartholomew's Hospital, London, UK.

Eva Wozniak (E)

Barts and London Genome Centre, School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.

David Klinzing (D)

Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Jyn Ling Kuan (JL)

Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Zenia Tiang (Z)

Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
ORCID: 0000-0003-1182-0023

Celso E Gomez Sanchez (CE)

G.V. (Sonny) Montgomery VA Medical Center and Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.

Per Hellman (P)

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Roger S Y Foo (RSY)

Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
ORCID: 0000-0002-8079-4618

Charles A Mein (CA)

Barts and London Genome Centre, School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.

Veronica A Kinsler (VA)

Cellular Pathology Department, Royal London Hospital, London, UK.

Peyman Björklund (P)

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Helen L Storr (HL)

Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.
ORCID: 0000-0002-9963-1931

Maria-Christina Zennaro (MC)

Université de Paris, PARCC, Inserm, Paris, France. maria-christina.zennaro@inserm.fr.
Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France. maria-christina.zennaro@inserm.fr.
ORCID: 0000-0001-5449-9191

Morris J Brown (MJ)

Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK. morris.brown@qmul.ac.uk.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. morris.brown@qmul.ac.uk.
ORCID: 0000-0001-8409-1082

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Somatic mutations of GNA11 and GNAQ in...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs de la surrénale › Tumeurs corticosurrénaliennes › Somatic mutations of GNA11 and GNAQ in...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs de la surrénale › Tumeurs corticosurrénaliennes › Adénome corticosurrénalien › Somatic mutations of GNA11 and GNAQ in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Somatic mutations of GNA11 and GNAQ in...
questionsmedicales.fr › Hormones corticosurrénaliennes › Hydroxycorticostéroïdes › 11-Hydroxycorticostéroïdes › Aldostérone › Somatic mutations of GNA11 and GNAQ in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines G hétérotrimériques › Sous-unités alpha des protéines G › Somatic mutations of GNA11 and GNAQ in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines G hétérotrimériques › Sous-unités alpha des protéines G › Sous-unités alpha Gq-G11 des protéines G › Somatic mutations of GNA11 and GNAQ in...
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questionsmedicales.fr › Maladies endocriniennes › Maladies des surrénales › Hypercorticisme › Hyperaldostéronisme › Somatic mutations of GNA11 and GNAQ in...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Développement sexuel › Climatère › Ménopause › Somatic mutations of GNA11 and GNAQ in...
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questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Somatic mutations of GNA11 and GNAQ in...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Somatic mutations of GNA11 and GNAQ in...