ArticleThe Journal of clinical endocrinology and metabolism2017
Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease.
Article in The Journal of clinical endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 4 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Targeted analysis of Ubiquitin-Specific Peptidase (USP8) in a population of Iranian people with Cushing's disease and a systematic review of the literature.BMC endocrine disorders · 2024Pooled it
- Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations.Nature reviews. Endocrinology · 2024Guideline
- Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways.International journal of molecular sciences · 2023Pooled it
- Cushing's disease due to somatic USP8 mutations: a systematic review and meta-analysis.Pituitary · 2019Pooled it
- Risk of recurrence after successful surgery for Cushing's disease and association with USP8 genotype and tumour size: an international, retrospective, longitudinal cohort study.The lancet. Diabetes & endocrinology · 2026Article
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Adrenal causes of endocrine hypertension in childhood or adolescence.Journal of endocrinological investigation · 2025Review
- Genetic evaluation of pediatric pituitary adenomas and USP8-related genotype-phenotype correlations in Cushing's disease.Pituitary · 2025Article
- Grading and staging for pituitary neuroendocrine tumors.Brain pathology (Zurich, Switzerland) · 2025Review
- Cushing's Disease Manifestation inInternational journal of molecular sciences · 2024Article
- Article
- Paediatric Cushing's disease: long-term outcome and predictors of recurrence.Frontiers in endocrinology · 2024Review
- Relevance of mutations in protein deubiquitinases genes andFrontiers in endocrinology · 2024Article
- Review
- [Molecular genetic abnormalities in ACTH-secreting pituitary tumors (corticotropinomas): fundamental research and prospects for use in clinical practice].Problemy endokrinologii · 2023Review
- An update on, and genetics of refractory adenomas of childhood.Pituitary · 2023Review
- Germline loss-of-functionmedRxiv : the preprint server for health sciences · 2023Article
- Germline loss-of-functionFrontiers in endocrinology · 2023Article
- Genetic drivers of Cushing's disease: Frequency and associated phenotypes.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Context: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as the most common genetic alteration in patients with Cushing disease (CD). However, the frequency of these mutations in the pediatric population has not been extensively assessed. Objective: We investigated the status of the USP8 gene at the somatic level in a cohort of pediatric patients with corticotroph adenomas. Design and Methods: The USP8 gene was fully sequenced in both germline and tumor DNA samples from 42 pediatric patients with CD. Clinical, biochemical, and imaging data were compared between patients with and without somatic USP8 mutations. Results: Five different USP8 mutations (three missense, one frameshift, and one in-frame deletion) were identified in 13 patients (31%), all of them located in exon 14 at the previously described mutational hotspot, affecting the 14-3-3 binding motif of the protein. Patients with somatic mutations were older at disease presentation [mean 5.1 ± 2.1 standard deviation (SD) vs 13.1 ± 3.6 years, P = 0.03]. Levels of urinary free cortisol, midnight serum cortisol, and adrenocorticotropic hormone, as well as tumor size and frequency of invasion of the cavernous sinus, were not significantly different between the two groups. However, patients harboring somatic USP8 mutations had a higher likelihood of recurrence compared with patients without mutations (46.2% vs 10.3%, P = 0.009). Conclusion: Somatic USP8 gene mutations are a common cause of pediatric CD. Patients harboring a somatic mutation had a higher likelihood of tumor recurrence, highlighting the potential importance of this molecular defect for the disease prognosis and the development of targeted therapeutic options.
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