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USP8 Mutations and Cell Cycle Regulation in Corticotroph Adenomas.
- Source :
-
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme [Horm Metab Res] 2020 Feb; Vol. 52 (2), pp. 117-123. Date of Electronic Publication: 2020 Feb 13. - Publication Year :
- 2020
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Abstract
- Corticotroph adenomas frequently harbor somatic USP8 mutations. These adenomas also commonly exhibit underexpression of P27, a cell cycle regulator. The present study aimed to determine the influence of USP8 mutations on clinical features of Cushing's disease and to elucidate the relationship between USP8 mutations and P27 underexpression in these tumors. Retrospective study with 32 patients with Cushing's disease was followed at the Ribeirao Preto Medical School University Hospital. We evaluated the patients' clinical data, the USP8 mutation status and the gene expression of cell cycle regulators P27/CDKN1B , CCNE1 , CCND1 , CDK2 , CDK4, and CDK6 in tumor tissue in addition to the protein expression of P27/CDKN1B . We observed somatic mutations in the exon 14 of USP8 in 31.3% of the patients. Larger tumor size was observed in patients harboring USP8 mutations (p=0.04), with similar rates of remission, age of presentation, salivary cortisol at 23:00 h and after 1 mg dexamethasone, ACTH levels, and early postoperative plasma cortisol. We observed no differences regarding the gene or protein expression of the cell cycle regulators according to USP8 mutation status. In this Brazilian series, the observed frequency of USP8 somatic mutations was similar to that reported in European ancestry populations. Although it was reasonable that USP8 mutations could contribute to cell cycle dysregulation and P27 underexpression in corticotroph adenomas, our data did not confirm this hypothesis. It is possible that increased deubiquitinase activity observed in mutated USP8 might influence other pathways related to cell growth and proliferation.<br />Competing Interests: The authors declare that they have no conflict of interest.<br /> (© Georg Thieme Verlag KG Stuttgart · New York.)
- Subjects :
- ACTH-Secreting Pituitary Adenoma physiopathology
Adolescent
Adrenocorticotropic Hormone blood
Adult
Brazil
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
Child
Endopeptidases metabolism
Endosomal Sorting Complexes Required for Transport metabolism
Exons
Female
Humans
Male
Middle Aged
Mutation
Pituitary ACTH Hypersecretion metabolism
Pituitary ACTH Hypersecretion physiopathology
Retrospective Studies
Ubiquitin Thiolesterase metabolism
Young Adult
ACTH-Secreting Pituitary Adenoma genetics
Cell Cycle
Endopeptidases genetics
Endosomal Sorting Complexes Required for Transport genetics
Pituitary ACTH Hypersecretion genetics
Ubiquitin Thiolesterase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1439-4286
- Volume :
- 52
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
- Publication Type :
- Academic Journal
- Accession number :
- 32053843
- Full Text :
- https://doi.org/10.1055/a-1089-7806