The Journal of clinical endocrinology and metabolism · 2012
Expression and mutations of KCNJ5 mRNA in Japanese patients with aldosterone-producing adenomas.
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Taguchi Ryo, Yamada Masanobu, Nakajima Yasuyo, Satoh Tetsurou, Hashimoto Koshi, Shibusawa Nobuyuki, Ozawa Atsushi, Okada Shuichi, Rokutanda Nana, Takata Daisuke, Koibuchi Yukio, Horiguchi Jun, Oyama Tetsunari, Takeyoshi Izumi, Mori Masatomo
Аннотация
CONTEXT: Mutations of the KCNJ5 gene have recently been identified in patients with aldosterone-producing adenomas (APA).
OBJECTIVE: Our objective was to investigate the expression and mutations of the KCNJ5 gene in Japanese patients with APA.
DESIGN AND PATIENTS: We sequenced KCNJ5 cDNA and measured KCNJ5 mRNA levels in 23 patients with APA operated on at Gunma University Hospital.
MAIN OUTCOME MEASURES: Mutations and mRNA levels of the KCNJ5 gene were examined and compared to those in cortisol-producing adenomas (Cushing's syndrome) and pheochromocytomas.
RESULTS: Of the 23 patients with APA, 15 (65.2%) had two somatic mutations of the KCNJ5 gene: 12 cases of p.G151R (eight with c.451G>A, and four with c.451G>C) and three cases of p.L168R (c.503T>G). Levels of KCNJ5 mRNA were significantly higher in the APA with mutations than those without. Immunohistochemistry also showed a stronger staining of KCNJ5 on the cell membrane in the tumor with a mutation. Furthermore, a PCR-restriction fragment length polymorphism assay with c.503T>G revealed the mutant mRNA to be expressed at a similar level to the wild type. The level of KCNJ5 mRNA in cortisol-producing adenomas was approximately 30% of that in APA, and almost no expression was observed in pheochromocytomas.
CONCLUSION: We found that: 1) a significant number of patients with APA had somatic mutations of the KCNJ5 gene; 2) KCNJ5 mRNA levels were higher in the APA with KCNJ5 mutations; and 3) the expression of KCNJ5 mRNA was significantly higher in APA than cortisol-producing adenomas and pheochromocytomas.
OBJECTIVE: Our objective was to investigate the expression and mutations of the KCNJ5 gene in Japanese patients with APA.
DESIGN AND PATIENTS: We sequenced KCNJ5 cDNA and measured KCNJ5 mRNA levels in 23 patients with APA operated on at Gunma University Hospital.
MAIN OUTCOME MEASURES: Mutations and mRNA levels of the KCNJ5 gene were examined and compared to those in cortisol-producing adenomas (Cushing's syndrome) and pheochromocytomas.
RESULTS: Of the 23 patients with APA, 15 (65.2%) had two somatic mutations of the KCNJ5 gene: 12 cases of p.G151R (eight with c.451G>A, and four with c.451G>C) and three cases of p.L168R (c.503T>G). Levels of KCNJ5 mRNA were significantly higher in the APA with mutations than those without. Immunohistochemistry also showed a stronger staining of KCNJ5 on the cell membrane in the tumor with a mutation. Furthermore, a PCR-restriction fragment length polymorphism assay with c.503T>G revealed the mutant mRNA to be expressed at a similar level to the wild type. The level of KCNJ5 mRNA in cortisol-producing adenomas was approximately 30% of that in APA, and almost no expression was observed in pheochromocytomas.
CONCLUSION: We found that: 1) a significant number of patients with APA had somatic mutations of the KCNJ5 gene; 2) KCNJ5 mRNA levels were higher in the APA with KCNJ5 mutations; and 3) the expression of KCNJ5 mRNA was significantly higher in APA than cortisol-producing adenomas and pheochromocytomas.
Предметные рубрики MeSH
Adrenal Cortex NeoplasmsAdrenal Gland NeoplasmsAdrenocortical AdenomaAdultAgedBase SequenceCross-Sectional StudiesCushing SyndromeFemaleG Protein-Coupled Inwardly-Rectifying Potassium ChannelsGenetic Association StudiesHumansHyperaldosteronismJapanMaleMiddle AgedMolecular Sequence DataMutationNeoplasm ProteinsPheochromocytomaRNA, MessengerRetrospective Studies