GH/PRL-secreting pituitary macroadenoma associated with &lt;i&gt;GNAS&lt;/i&gt; p.Gln227Leu mutation: pediatric case report and review

Watanabe, Daisuke; Yagasaki, Hideaki; Kojika, Satoru; Ogiwara, Masakazu; Kinouchi, Hiroyuki; Nakane, Takaya; Inukai, Takeshi

doi:10.1507/endocrj.ej18-0370

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…Current treatment regimens for pituitary tumors involve the use hormones, which limits applications for the treatment of prolactinoma (25). Pituitary tumors secrete PRL and GH, which can cause additional physiological effects (26,27). Therefore, it is of great significance to identify novel targets for the diagnosis and treatment of prolactinoma.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑29‑3p regulates the β‑catenin pathway by targeting IGF1 to inhibit the proliferation of prolactinoma cells

Xia

et al. 2021

Mol Med Rep

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The present study aimed to analyze the effects and underlying mechanisms of microRNA (miR)-29-3p on the proliferation and secretory abilities of prolactinoma cells by targeting insulin-like growth factor (IGF)-1/β-catenin. The relationship between miR-29a-3p and the survival of prolactinoma cells was analyzed with the Kaplan-Meier method in reference to The Cancer Genome Atlas. The expression levels of miR-29a-3p and IGF-1 in MMQ and GH3 cells were detected. A dual-luciferase reporter gene assay was performed to verify the combination of miR-29a-3p and IGF-1. Cells were transfected with a miR-29a-3p mimic and/or IGF-1 pcDNA3.1 to analyze the effects on the proliferation, apoptosis and secretion of prolactin (PRL) and growth hormone (GH) of prolactinoma cells. The effects on β-catenin in the cytoplasm and nucleus were investigated by western blot analysis. The results showed that miR-29a-3p expression was low in MMQ and GH3 cells. Overexpression miR-29a-3p inhibited IGF-1 mRNA and protein expression. miR-29a-3p inhibited cell proliferation and PRL and GH expression, and promoted apoptosis by inhibiting IGF-1. Increasing the expression of miR-29a-3p increased β-catenin levels in the cytoplasm, whereas IGF-1 promoted β-catenin activation and entry into the nucleus, and reversed the inhibitory effects of miR-29a-3p on β-catenin. To conclude, miR-29a-3p inhibited the proliferation and secretory abilities of prolactinoma cells by inhibiting nuclear translocation of β-catenin via a molecular mechanism that is inseparable from IGF-1.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑29‑3p regulates the β‑catenin pathway by targeting IGF1 to inhibit the proliferation of prolactinoma cells

Xia

et al. 2021

Mol Med Rep

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“…In X-LAG, duplications in the Xq26.3 region lead to enhanced GPR101 gene expression via disruption of the topologically associating domain (TAD) surrounding the gene, so X-LAG represents a TADopathy 81 . Mosaic mutations have been seen in GNAS (McCune-Albright syndrome) and GPR101 (in boys), whereas somatic GNAS mutations restricted to the pituitary are rare in CYP unlike in adults, where they have been identified in 20-40% of tumour samples [82][83][84] . In CYP with GH-secreting adenoma, AIP mutations (29% of patients with gigantism) and duplication in GPR101 (10%) occur most frequently, followed by McCune-Albright syndrome (5%), Carney complex (1%), MEN1 (1%) 79 and, rarely, MEN1like disease or phaeochromocytoma-paraganglioma-related gene alterations.…”

Section: Geneticsmentioning

confidence: 99%

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations

Korbonits,

Blair,

Boguslawska

et al. 2024

Nat Rev Endocrinol

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Tumours of the anterior part of the pituitary gland represent just 1% of all childhood (aged <15 years) intracranial neoplasms, yet they can confer high morbidity and little evidence and guidance is in place for their management. Between 2014 and 2022, a multidisciplinary expert group systematically developed the first comprehensive clinical practice consensus guideline for children and young people under the age 19 years (hereafter referred to as CYP) presenting with a suspected pituitary adenoma to inform specialist care and improve health outcomes. Through robust literature searches and a Delphi consensus exercise with an international Delphi consensus panel of experts, the available scientific evidence and expert opinions were consolidated into 74 recommendations. Part 1 of this consensus guideline includes 17 pragmatic management recommendations related to clinical care, neuroimaging, visual assessment, histopathology, genetics, pituitary surgery and radiotherapy. While in many aspects the care for CYP is similar to that of adults, key differences exist, particularly in aetiology and presentation. CYP with suspected pituitary adenomas require careful clinical examination, appropriate hormonal work-up, dedicated pituitary imaging and visual assessment. Consideration should be given to the potential for syndromic disease and genetic assessment. Multidisciplinary discussion at both the local and national levels can be key for management. Surgery should be performed in specialist centres. The collection of outcome data on novel modalities of medical treatment, surgical intervention and radiotherapy is essential for optimal future treatment. Sections Developing recommendationsWhere there was sufficient moderate-quality evidence to answer the PICO questions, the GDG originally made 54 recommendations whose strength was determined using the GRADE criteria 20 by a trade-off between benefits and harms given the quality of the underpinning evidence. Where the evidence base was lacking, of low quality, conflicting or largely extrapolated from adult experiences, the GDG formulated consensus recommendations and submitted these to experts outside the GDG (the international Delphi consensus panel, Supplementary Table 2) in three rounds of a Delphi consensus process (first round,

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“…In general, most studies suggest that GNAS mutations are associated with densely granulated somatotroph tumors, and the efficacy of first-generation SSA is higher [ 29 ]. However, controversy remains with regards to the association between GNAS mutations and pathological subtype, and a small number of cases exhibit the atypical phenotype including young age, macroadenoma, invasiveness and resistance to SSA and dopamine agonist (DA) [ 30 , 31 , 32 ].…”

Section: Genetic Pathogenesis In Sporadic Somatotroph Tumorsmentioning

confidence: 99%

Genetic and Epigenetic Pathogenesis of Acromegaly

Yamamoto

Takahashi

2022

Cancers

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Acromegaly is caused by excessive secretion of GH and IGF-I mostly from somatotroph tumors. Various genetic and epigenetic factors are involved in the pathogenesis of somatotroph tumors. While somatic mutations of GNAS are the most prevalent cause of somatotroph tumors, germline mutations in various genes (AIP, PRKAR1A, GPR101, GNAS, MEN1, CDKN1B, SDHx, MAX) are also known as the cause of somatotroph tumors. Moreover, recent findings based on multiple perspectives of the pangenomic approach including genome, transcriptome, and methylome analyses, histological characterization, genomic instability, and possible involvement of miRNAs have gradually unveiled the whole landscape of the underlying mechanisms of somatotroph tumors. In this review, we will focus on the recent advances in genetic and epigenetic pathogenesis of somatotroph tumors.

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GH/PRL-secreting pituitary macroadenoma associated with <i>GNAS</i> p.Gln227Leu mutation: pediatric case report and review

Cited by 4 publications

References 27 publications

MicroRNA‑29‑3p regulates the β‑catenin pathway by targeting IGF1 to inhibit the proliferation of prolactinoma cells

MicroRNA‑29‑3p regulates the β‑catenin pathway by targeting IGF1 to inhibit the proliferation of prolactinoma cells

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations

Genetic and Epigenetic Pathogenesis of Acromegaly

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