Endocrinol Metab.  2017 Sep;32(3):332-338. 10.3803/EnM.2017.32.3.332.

CTNNB1 Mutation in Aldosterone Producing Adenoma

• Wang JJ
• Peng KY
• Wu VC
• Tseng FY
• Wu KD

• KMID: 2389813
• DOI: http://doi.org/10.3803/EnM.2017.32.3.332

Abstract

Discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas (APAs) with distinct clinical presentations and pathological features. Catenin β1 (CTNNB1) mutation in APAs has been recently described and discussed in the literature. However, significant knowledge gaps still remain regarding the prevalence, clinical characteristics, pathophysiology, and outcomes in APA patients harboring CTNNB1 mutations. Aberrant activation of the Wnt/β-catenin signaling pathway will further modulate tumorigenesis. We also discuss the recent knowledge of CTNNB1 mutation in adrenal adenomas.

Keyword

CBTNN1; KCNJ5; Primary aldosteronism; Aldosterone producing adenomas; Taiwan Primary Aldosteronism Investigator

MeSH Terms

Adenoma*
Aldosterone*
Carcinogenesis
Humans
Prevalence
Aldosterone

Figure

• 

  Fig. 1 The prevalence of the most known mutation of aldosterone producing adenoma. This box plot displays the full range of variation (from maximum, mean, medium to minimum, accordingly) in each index somatic mutation. CACNA1D, calcium voltage-gated channel subunit α1 D; KCNJ5, potassium voltage-gated channel subfamily J member 5; ATP2B3, ATPase plasma membrane Ca2+ transporting 3; ATP1A1, ATPase Na+/K+ transporting subunit α1; GNAS, guanine nucleotide binding protein, α stimulating; CTNNB1, catenin β1.

• 

  Fig. 2 A two-hit model for the pathogenesis of aldosterone-producing adenoma (APA). (A, B) Primary hit: Somatic mutations in CACNA1D, KCNJ5, ATP2B3, ATP1A1, and possibly other genetic alterations produce cell depolarization, increased cytoplasmic calcium level and increased CYP11B2 expression, causing aldosterone hypersecretion. Secondary hit: Aberrant activation of signaling pathways (such as Wnt/β-catenin, Shh, PKA, etc.) causes imbalances between cell proliferation and death in the adrenal, leading to adenoma formation. (A) Adapted from Lalli et al., with permission from Elsevier [36]. (B) Adapted from Seidel et al. [37]. CACNA1D, calcium voltage-gated channel subunit α1 D; KCNJ5, potassium voltage-gated channel subfamily J member 5; ATP2B3, ATPase plasma membrane Ca2+ transporting 3; ATP1A1, ATPase Na+/K+ transporting subunit α1; APCC, aldosterone-producing cell clusters; HSD3b, hydroxy-δ-5-steroid dehydrogenase, 3β- and steroid δ-isomerase cluster; CTNNB1, catenin β1; DACH1, dachshund family transcription factor 1; Shh, sonic hedgehog; PKA, protein kinase A; Ang II, angiotensin II; AT1, Ang II type 1; CAMK, Ca2+/calmodulin-dependent protein kinase; CYP11B2, cytochrome P450 family 11 subfamily B member 2.

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