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Corticotroph adenomas frequently harbor somatic mutations. These adenomas also commonly exhibit underexpression of P27, a cell cycle regulator. The present study aimed to determine the influence of mutations on clinical features of Cushing's disease and to elucidate the relationship between 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 mutation status and the gene expression of cell cycle regulators , , , , and in tumor tissue in addition to the protein expression of P27/CDKN1B We observed somatic mutations in the exon 14 of in 31.3% of the patients. Larger tumor size was observed in patients harboring 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 mutation status. In this Brazilian series, the observed frequency of somatic mutations was similar to that reported in European ancestry populations. Although it was reasonable that 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 might influence other pathways related to cell growth and proliferation.
This article was published in the following journal.
Name: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
Objective Pituitary corticotroph adenomas commonly cause Cushing's disease (CD) but part of these tumours are hormonally inactive (silent corticotroph adenomas, SCA). USP8 mutations are well known dri...
Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas having ubiquitin-specific protease 8 (USP8) mutations. Aims we...
Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors has been a matter of interes...
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A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.
A NIMA-related kinase that functions in CELL CYCLE regulation, the control of CILIA assembly, and CENTROSOME duplication. It is activated at G2 PHASE CELL CYCLE CHECKPOINTS in response to DNA DAMAGE.
ATP-dependent DNA helicase that contains two N-terminal ZINC FINGERS and C-terminal ATP-binding and helicase domains. It functions in the regulation of gene transcription and CHROMATIN REMODELING. ATRX undergoes cell-cycle dependent phosphorylation, which causes it to translocate from the NUCLEAR MATRIX to CHROMATIN; thus, it may change its role from gene regulation during INTERPHASE to ensuring proper chromosome segregation at MITOSIS. Mutations in the ATRX gene are associated with cases of X-LINKED MENTAL RETARDATION co-morbid with ALPHA-THALASSEMIA (ATRX syndrome).
A serine/threonine-specific protein kinase which is encoded by the CHEK1 gene in humans. Checkpoint kinase 1 (also known as Chk1) coordinates DNA damage response and cell cycle checkpoint response. Under these conditions, activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death, to prevent damaged cells from progressing through the cell cycle.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...