Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas

Dutta, Ravi Kumar; Welander, Jenny; Brauckhoff, Michael; Walz, Martin K.; Alesina, Pier Francesco; Arnesen, Thomas; Söderkvist, Peter; Gimm, Oliver

doi:10.1530/erc-13-0466

Cited by 27 publications

(30 citation statements)

References 10 publications

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“…Since the discovery of the KCNJ5 mutations in APAs by Choi and coworkers, there have been several confirmative reports from different research groups worldwide (Boulkroun et al 2012, Taguchi et al 2012, Dutta et al 2014, Fernandes-Rosa et al 2014, Murthy et al 2014. Fernandes-Rosa and coworkers sequenced the hot spot region in 474 APAs collected from the European Network for the Study of Adrenal Tumor (ENSAT).…”

Section: Kcnj5mentioning

confidence: 98%

“…Azizan et al 2012a, Azizan et al 2013, Beuschlein et al 2013, Dutta et al 2014, Zilbermint et al 2015, Scholl et al 2015b. APAs may occur in patients of all ages, but a high prevalence is seen in patients 40-50 years of age.…”

Section: :10mentioning

confidence: 99%

“…ATP2B3, CTNNB1, CACNA1D, CACNA1H and ARMC5 (Choi et al 2011, Azizan et al 2012a, Taguchi et al 2012, Beuschlein et al 2013, Dutta et al 2014, Zilbermint et al 2015, Scholl et al 2015b). So far, these identified genes are mutated in approximately 60% of patients with APAs.…”

Section: :10mentioning

confidence: 99%

“…While critically analyzing data from previous publications concerning the age of patients and size of tumors between males and females, irrespective of mutational status (Choi et al 2011, Dutta et al 2014, Akerstrom et al 2015, Scholl et al 2015a, it became obvious that the majority of females were younger and had not entered menopause (<50 years (N = 56) vs >50 years (N = 26), P = 0.0001). Although there was no size difference in the tumors before or after menopause, the aldosterone-to-renin ratio was higher before initiation of menopause (289.5 ± 44.2 (N = 56) vs 204.1 ± 42.7 (N = 26), P = 0.26 (mean ± s.e.m)).…”

Section: Figurementioning

confidence: 99%

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Genetics of primary hyperaldosteronism

Dutta

Söderkvist

Gimm

2016

Endocrine-Related Cancer

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Hypertension is a common medical condition and affects approximately 20% of the population in developed countries. Primary aldosteronism is the most common form of secondary hypertension and affects 8-13% of patients with hypertension. The two most common causes of primary aldosteronism are aldosterone-producing adenoma and bilateral adrenal hyperplasia. Familial hyperaldosteronism types I, II and III are the known genetic syndromes, in which both adrenal glands produce excessive amounts of aldosterone. However, only a minority of patients with primary aldosteronism have one of these syndromes. Several novel susceptibility genes have been found to be mutated in aldosterone-producing adenomas: KCNJ5, ATP1A1, ATP2B3, CTNNB1, CACNA1D, CACNA1H and ARMC5. This review describes the genes currently known to be responsible for primary aldosteronism, discusses the origin of aldosterone-producing adenomas and considers the future clinical implications based on these novel insights.

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Section: Kcnj5mentioning

confidence: 98%

Section: :10mentioning

confidence: 99%

Section: :10mentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Genetics of primary hyperaldosteronism

Dutta

Söderkvist

Gimm

2016

Endocrine-Related Cancer

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“…However, what is more surprising is that two novel ATP2B3 mutations have recently been found in tissue from a number of aldosterone-producing adenomas (APAs), a major factor in the development of primary aldosteronism which is the most common cause of secondary hypertension (27). Since Beuschlein et al's first report in 2013 (27), ATP2B3 mutations have been identified in APAs present in western European, Japanese, Taiwanese, Chinese, and American populations occurring at frequencies ranging from 0.6 to 9% (6,102,121,186,272,330,331,396,404,422). With the exception of one Taiwanese patient who exhibited a Tyr410Asp substitution (404), all mutations identified thus far involve the deletion of one or more amino acids between Thr-423 and Leu-433 lying in the M4 region of the plasma membrane, believed to be important in Ca 2ϩ binding during its transport to the extracellular space.…”

Section: Pmca3 Cerebellar Ataxia and Adenomamentioning

confidence: 99%

The Plasma Membrane Calcium ATPasesand Their Role as Major New Players in Human Disease

Stafford

Wilson

Oceandy

et al. 2017

Physiological Reviews

110

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The Ca2+ extrusion function of the four mammalian isoforms of the plasma membrane calcium ATPases (PMCAs) is well established. There is also ever-increasing detail known of their roles in global and local Ca2+ homeostasis and intracellular Ca2+ signaling in a wide variety of cell types and tissues. It is becoming clear that the spatiotemporal patterns of expression of the PMCAs and the fact that their abundances and relative expression levels vary from cell type to cell type both reflect and impact on their specific functions in these cells. Over recent years it has become increasingly apparent that these genes have potentially significant roles in human health and disease, with PMCAs1-4 being associated with cardiovascular diseases, deafness, autism, ataxia, adenoma, and malarial resistance. This review will bring together evidence of the variety of tissue-specific functions of PMCAs and will highlight the roles these genes play in regulating normal physiological functions and the considerable impact the genes have on human disease.

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5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer

Kirschner

Stratakis

2015

HORM CANC

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Genetic tools for the analysis of human tumors have developed rapidly over the past 20 years. Adrenocortical neoplasms have been subject to multiple analyses using these new genetic tools. Analysis of adrenocortical carcinomas (ACCs) has been complicated by the fact that these tumors tend to exhibit multiple somatic abnormalities, so that identifying driver mutations is complex task. In contrast, benign adrenocortical neoplasms have proven to be a fertile ground for the identification of the genetic causes of adrenocortical adenomas, as well as a variety of adrenocortical hyperplasia. Analysis of cortisol-producing adrenocortical adenomas has revealed alterations leading to enhanced signaling through the cAMP-dependent protein kinase (PKA) pathway. In contrast, macronodular cortisol-producing neoplasias have been shown to result from mutations in the ARMC5 gene, whose function is not yet quite so clear. In contrast, adrenal tumors resulting in excess production of the blood pressure hormone aldosterone almost always result from abnormalities of calcium handling, both in single adenomas and in bilateral hyperplasias. In both cases, there is elevation of a signaling pathway responsible both for hormone secretion and for gland growth and maintenance, thus confirming the linkage of these two output of cellular physiology. The connection between the benign hyperplasia observed in these states and adrenocortical carcinogenesis is not nearly as clear, although genetic studies are beginning to elucidate the relationship between benign and malignant tumors of this gland.

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Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas

Abstract: n/

Cited by 27 publications

References 10 publications

Genetics of primary hyperaldosteronism

Genetics of primary hyperaldosteronism

The Plasma Membrane Calcium ATPasesand Their Role as Major New Players in Human Disease

5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer

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