Different Somatic Mutations in Multinodular Adrenals With Aldosterone-Producing Adenoma.
Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D are found in aldosterone-producing adenoma. In addition, adrenals with aldosterone-producing adenomas show cortical remodeling and frequently multiple secondary nodules. Our aim was to investigate whether different aldosterone-producing nodules from the same adrenal share the same mutational status. Aldosterone synthase expression was assessed in multinodular adrenals from 27 patients. DNA of 37 aldosterone-producing secondary nodules was extracted from formalin-fixed paraffin-embedded tissues and genotyped for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations. Among 17 adrenals with a somatic mutation in the principal nodule, 4 showed the same mutation in a secondary nodule, whereas 10 had no mutation in any of the known genes. In 1 adrenal harboring the KCNJ5 p.Gly151Arg mutation in the principal nodule, the same mutation was present in 2 secondary nodules, but no mutation was found in a third nodule. Finally, in 2 adrenals with a CACNA1D mutation in the principal nodule, a KCNJ5 mutation was identified in the secondary nodule. Among 10 adrenals without mutations in the principal nodule, 1 carried a KCNJ5 mutation in the secondary nodule. No mutations were detected in 7 aldosterone-producing cell clusters from 6 adrenals. No association was observed between the presence of mutations in secondary nodules and clinical parameters. In conclusion, different mutations are found in different aldosterone-producing nodules from the same adrenal, suggesting that somatic mutations are independent events triggered by mechanisms that remain to be identified.
From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Service de Génétique (F.L.F.-R., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS (C.E.G.-S.).
Fabio Luiz
FL
Fernandes-Rosa
From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Service de Génétique (F.L.F.-R., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS (C.E.G.-S.).
Isabelle
I
Giscos-Douriez
From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Service de Génétique (F.L.F.-R., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS (C.E.G.-S.).
Laurence
L
Amar
From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Service de Génétique (F.L.F.-R., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS (C.E.G.-S.).
Celso E
CE
Gomez-Sanchez
From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Service de Génétique (F.L.F.-R., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS (C.E.G.-S.).
Tchao
T
Meatchi
From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Service de Génétique (F.L.F.-R., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS (C.E.G.-S.).
Sheerazed
S
Boulkroun
From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., I.G.-D., L.A., T.M., S.B., M.-C.Z.); Service de Génétique (F.L.F.-R., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; and Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS (C.E.G.-S.). maria-christina.zennaro@inserm.fr.
Maria-Christina
MC
Zennaro
D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D000483:Alleles; D020746:Calcium Channels, L-Type / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics*; D012189:Retrospective Studies; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase
adrenal cortex; aldosterone; hyperaldosteronism; mineralocorticoids; mutation; potassium channels