Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome

Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Deméocq, Vianney; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Éric; Guiochon‐Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Henri; Herder, Wouter W. de; Louiset, Estelle; Lacroix, André; Chanson, Philippe; Bouligand, Jérôme; Kamenický, Peter

doi:10.1016/j.ando.2018.04.002

Cited by 9 publications

(9 citation statements)

References 26 publications

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“…At present in PBMAH, no genetic alteration has been given to explain the mechanism of illegitimate membrane receptors despite whole genome approaches [ 63 ]. However, in unilateral adenoma with GIPR ectopic expression, gene rearrangement has been recently found at the GIPR locus [ 64 ].…”

Section: Adrenal Cushing Syndromementioning

confidence: 99%

Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome

Vaduva

Bonnet

Bertherat

2020

Journal of the Endocrine Society

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This review reports the main molecular alterations leading to development of benign cortisol and/or aldosterone secreting adrenal tumors. Causes of adrenal Cushing can be divided in two groups: multiple bilateral tumors or adenomas secreting cortisol. Bilateral causes are mainly Primary Pigmented Nodular Adrenocortical Disease (PPNAD), most of the time due to PRKAR1A germline inactivating mutations, and Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH), that can be caused in some rare syndromic cases by germline inactivating mutations of MEN1, APC and FH and of ARMC5 in isolated forms. PRKACA somatic activating mutations are the main alterations in unilateral cortisol producing adenomas (CPA). In primary hyperaldosteronism (PA), familial forms were identified in 1-5% of cases: familial hyperaldosteronism type I (FH-I) due to a chimeric CYP11B1/CYP11B2 hybrid gene, FH-II due to CLCN-2 germline mutations, FH-III due to KCNJ5 germline mutations, FH-IV due to CACNA1H germline mutations and PA, seizures and neurological abnormalities (PASNA) syndrome due to CACNA1D germline mutations. Several somatic mutations have been found in aldosterone producting adenomas (APAs) in KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1 genes.

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Section: Adrenal Cushing Syndromementioning

confidence: 99%

Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome

Vaduva

Bonnet

Bertherat

2020

Journal of the Endocrine Society

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“…A recent study identified somatic duplications of the 19q13.32 chromosomal region, including the GIPR gene, in 3/14 patients with GIP-dependent CS. 31 In two of these cases, rearrangements favoring the monoallelic expression of GIPR were identified, and among the genes contained in the amplified region, only GIPR was consistently overexpressed in the adrenocortical lesions. GIPR overexpression leads to increased steroidogenesis via overactivation of the cAMP/PKA pathway.…”

Section: Genetic Alterations In Cushing’s Syndrome Of Adrenal Originmentioning

confidence: 96%

Genetics of Cushing’s Syndrome

Hernández-Ramírez¹,

Stratakis²

2018

Endocrinology and Metabolism Clinics of North America

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The knowledge on the molecular and genetic causes of Cushing's syndrome (CS) has greatly increased in the recent years. Somatic mutations leading to overactive 3',5'-cyclic adenosine monophosphate/protein kinase A and wingless-type MMTV integration site family/beta-catenin pathways are the main molecular mechanisms underlying adrenocortical tumorigenesis. Corticotropinomas are characterized by resistance to glucocorticoid negative feedback, impaired cell cycle control and overexpression of pathways sustaining ACTH secretion. Recognizing the genetic defects behind corticotroph and adrenocortical tumorigenesis proves crucial for tailoring the clinical management of CS patients and for designing strategies for genetic counseling and clinical screening to be applied in routine medical practice.

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“…In a rare form of FDCS, glucocorticoid excess is driven by aberrant glucose-dependent insulinotropic polypeptide receptor (GIPR) expression that arise from somatic duplications (within the adrenal lesions) in chromosome region 19q13.32 containing the GIPR locus [45]. GIP-dependent PBMAH should be distinguished from FDCS.…”

Section: Macronodular Adrenocortical Hyperplasiamentioning

confidence: 99%

A Gene-Based Classification of Primary Adrenocortical Hyperplasias

Hannah‐Shmouni

Stratakis

2020

Horm Metab Res

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Primary or adrenocorticotropin-independent adrenocortical tumors and hyperplasias represent a heterogeneous group of adrenocortical neoplasms that arise from various genetic defects, either in isolation or familial. The traditional classification as adenomas, hyperplasias, and carcinomas is non-specific. The recent identification of various germline and somatic genes in the development of primary adrenocortical hyperplasias has provided important new insights into the molecular pathogenesis of adrenal diseases. In this new era of personalized care and genetics, a gene-based classification that is more specific is required to assist in the understanding of their disease processes, hormonal functionality and signaling pathways. Additionally, a gene-based classification carries implications for treatment, genetic counseling and screening of asymptomatic family members. In this review, we discuss the genetics of benign adrenocorticotropin-independent adrenocortical hyperplasias, and propose a new gene-based classification system and diagnostic algorithm that may aid the clinician in prioritizing genetic testing, screening and counseling of affected, at risk individuals and their relatives.

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Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome

Cited by 9 publications

References 26 publications

Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome

Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome

Genetics of Cushing’s Syndrome

A Gene-Based Classification of Primary Adrenocortical Hyperplasias

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