HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: GPR101, an orphan GPCR with roles in growth and pituitary tumorigenesis

Trivellin, Giampaolo; Faucz, Fábio R.; Daly, Adrian; Beckers, Albert; Stratakis, Constantine A.

doi:10.1530/erc-20-0025

Cited by 14 publications

(9 citation statements)

References 65 publications

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“…The GPR101 gene encodes a class A, rhodopsin-like, orphan G protein-coupled receptor (GPCR) [30][31][32]. GPR101 protein was found to be strongly expressed in the human normal pituitary during fetal development as well as in adolescence but not in adult pituitary, suggesting that its expression is induced during development and adolescence [33].…”

Section: Gpr101mentioning

confidence: 99%

Pituitary Tumors: Genetic and Molecular Factors Underlying Pathogenesis and Clinical Behavior

Spada¹,

Mantovani²,

Treppiedi³

et al. 2021

Neuroendocrinology

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Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neoplasms. Although generally benign, they can show a clinically aggressive course, with local invasion, recurrences and resistance to medical treatment. No universally accepted biomarkers of aggressiveness are available yet, and predicting clinical behavior of PitNETs remains a challenge. In rare cases the presence of germline mutations in specific genes predisposes to PitNETs formation, as part of syndromic diseases or familial isolated pituitary adenomas (FIPA), and associates to more aggressive, invasive and drug resistant tumors. The vast majority of cases is represented by sporadic PitNETs. Somatic mutations in the  subunit of stimulatory G protein gene (gsp) and in the ubiquitin-specific protease 8 (USP8) gene have been recognized as pathogenetic factors in sporadic GH- and ACTH-secreting PitNETs, respectively, without an association with a worse clinical phenotype. Other molecular factors have been found to significantly affect PitNETs drug responsiveness and invasive behavior. These molecules are cytoskeleton and/or scaffold proteins whose alterations prevent proper functioning of the somatostatin and dopamine receptors, targets of medical therapy, or promote the ability of tumor cells to invade surrounding tissues. The aim of the present review is to provide an overview of the genetic and molecular alterations that can contribute to determine PitNETs clinical behavior. Understanding subcellular mechanisms underlying pituitary tumorigenesis and PitNETs clinical phenotype will hopefully lead to identification of new potential therapeutic targets and new markers predicting the behavior and the response to therapeutic treatments of PitNETs.

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Section: Gpr101mentioning

confidence: 99%

Pituitary Tumors: Genetic and Molecular Factors Underlying Pathogenesis and Clinical Behavior

Spada¹,

Mantovani²,

Treppiedi³

et al. 2021

Neuroendocrinology

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“…Furthermore, acromegaly can present as a familial isolated pituitary tumor (FIPA), often due to mutations in the aryl hydrocarbon receptor-interacting peptide (AIP) gene (2). More recently, few cases of X-linked acrogigantism (X-LAG) have been described, as well (3).…”

Section: Introductionmentioning

confidence: 99%

Global epidemiology of acromegaly: a systematic review and meta-analysis

Crisafulli

Luxi

Sultana

et al. 2021

European Journal of Endocrinology

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Objective: To date, no systematic reviews and meta-analysis on the global epidemiology of acromegaly are available in literature. The aims of this study are to provide a systematic review and a meta-analysis of the global epidemiology of acromegaly and to evaluate the quality of study reporting for the identified studies. Methods: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies assessing the epidemiology of acromegaly from inception until 31st January 2020. We included original observational studies written in English, reporting acromegaly prevalence and/or incidence for a well-defined geographic area. Two reviewers independently extracted data and performed quality assessments. Prevalence and incidence pooled estimates were derived performing a random-effects meta-analysis. Results: A total of 32 studies were included in the systematic review, and 22 of them were included in the meta-analysis. The pooled prevalence of acromegaly was 5.9 (95%CI: 4.4-7.9) per 100,000 persons, while the incidence rate (IR) was 0.38 (95%CI: 0.32-0.44) cases per 100,000 person-years. For both prevalence and IR, a considerable between-study heterogeneity was found (I2= 99.3% and 86.0%, respectively). The quality of study reporting was rated as medium for 20 studies and low for 12 studies. Conclusions: Although the largest amount of heterogeneity was due to the high precision of the studies’ estimates, data source and geographic area could represent relevant study-levels factors which could explain about 50% of the total between-study variability. Large-scale high quality studies on the epidemiology of acromegaly are warranted to help the public health system in making decisions.

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“…X-LAG syndrome is exceptionally rare, with only 40 patients described ( 301 ). Most occur sporadically due to constitutional duplications in females or somatic mosaicism in males.…”

Section: Clinical Spectrummentioning

confidence: 99%

Clinical Biology of the Pituitary Adenoma

et al. 2022

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All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology, and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in ten percent of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intra-pituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas and particularly their benign nature stands in marked contrast to other tumors of the endocrine system such as thyroid and neuroendocrine tumors.

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HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: GPR101, an orphan GPCR with roles in growth and pituitary tumorigenesis

Cited by 14 publications

References 65 publications

Pituitary Tumors: Genetic and Molecular Factors Underlying Pathogenesis and Clinical Behavior

Pituitary Tumors: Genetic and Molecular Factors Underlying Pathogenesis and Clinical Behavior

Global epidemiology of acromegaly: a systematic review and meta-analysis

Clinical Biology of the Pituitary Adenoma

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