ArticleNeuro-oncology2019
Driver mutations in USP8 wild-type Cushing's disease.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
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Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Pooled it
- The Role of Activation of PI3K/AKT/mTOR and RAF/MEK/ERK Pathways in Aggressive Pituitary Adenomas-New Potential Therapeutic Approach-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Ubiquitin Specific Peptidase 48 Deubiquitinates METTL3 to Modulate Ferroptosis in Gastric Cancer Cells.Molecular carcinogenesis · 2026Article
- Multi-omics integration unravels four molecular subgroups of corticotroph pituitary neuroendocrine tumours with distinct clinicopathological features.Nature communications · 2026Article
- The value of targeting CXCR4 withEuropean journal of nuclear medicine and molecular imaging · 2026Article
- Deubiquitinase USP8 regulates the spindle assembly checkpoint in oocytes.Science advances · 2026Article
- Molecular biology of pituitary neuroendocrine tumors.Journal of neuro-oncology · 2026Review
- New Insights from the Expression of the Mismatch Repair System in Pituitary Neuroendocrine Tumors.Endocrine pathology · 2026Article
- Differential expression of POMC-processing genes in corticotroph tumors.Endocrine oncology (Bristol, England) · 2026Article
- Article
- The PitNET Puzzle: From Zero to Linking Molecular Behavior with Neurosurgical Aspects.Medicina (Kaunas, Lithuania) · 2025Review
- USP8, USP48, BRAF and TP53 mutations in crooke cell adenoma.Pituitary · 2025Article
- Endocrine cancer organoids in basic and translational medical research.Science China. Life sciences · 2025Review
- Clinical presentation, predictive factors and management of patients with Nelson syndrome: a retrospective study.Pituitary · 2025Article
- Management of Cushing's disease in the initial phase~From detection to surgery~.Endocrine journal · 2025Review
- Clinical Implications of Molecular and Genetic Biomarkers in Cushing's Disease: A Literature Review.Journal of clinical medicine · 2025Review
- A Brief Overview of Molecular Biology in Pituitary Adenomas with a Focus on Aggressive Lesions.International journal of molecular sciences · 2025Review
- Cushing syndrome.Nature reviews. Disease primers · 2025Review
- The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors.Brain pathology (Zurich, Switzerland) · 2025Review
- Grading and staging for pituitary neuroendocrine tumors.Brain pathology (Zurich, Switzerland) · 2025Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMedical treatment in Cushing's disease (CD) is limited due to poor understanding of its pathogenesis. Pathogenic variants of ubiquitin specific peptidase 8 (USP8) have been confirmed as causative in around half of corticotroph tumors. We aimed to further characterize the molecular landscape of those CD tumors lacking USP8 mutations in a large cohort of patients.
methodsExome sequencing was performed on 18 paired tumor-blood samples with wild-type USP8 status. Candidate gene variants were screened by Sanger sequencing in 175 additional samples. The most frequent variant was characterized by further functional in vitro assays.
resultsRecurrent somatic hotspot mutations in another deubiquitinase, USP48, were found in 10.3% of analyzed samples. Several possibly damaging variants were found in TP53 in 6 of 18 samples. USP48 variants were associated with smaller tumors and trended toward higher frequency in female patients. They also changed the structural conformation of USP48 and increased its catalytic activity toward its physiological substrates histone 2A and zinc finger protein Gli1, as well as enhanced the stimulatory effect of corticotropin releasing hormone (CRH) on pro-opiomelanocortin production and adrenocorticotropic hormone secretion.
conclusionsUSP48 pathogenic variants are relatively frequent in USP8 wild-type tumors and enhance CRH-induced hormone production in a manner coherent with sonic hedgehog activation. In addition, TP53 pathogenic variants may be more frequent in larger CD tumors than previously reported.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.