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Updated: Dec 28, 2025

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USP8 Mutations and Cell Cycle Regulation in Corticotroph Adenomas

Clarissa Silva Martins1, Renata Costa Camargo1, Fernanda Borchers Coeli-Lacchini1

  • 1Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme
|February 14, 2020
PubMed

Insights

Somatic USP8 mutations in corticotroph adenomas are linked to larger tumor size but not P27 underexpression. This study in Cushing's disease patients found USP8 mutations influence tumor growth, but not cell cycle regulator expression.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Corticotroph adenomas, a common cause of Cushing's disease, frequently harbor somatic USP8 mutations.
  • These tumors often show underexpression of P27, a key cell cycle regulator.

Purpose of the Study:

  • To investigate the clinical impact of USP8 mutations in Cushing's disease.
  • To determine the relationship between USP8 mutations and P27 underexpression in corticotroph adenomas.

Main Methods:

  • Retrospective study of 32 Cushing's disease patients.
  • Analysis of USP8 mutation status, clinical data, and gene/protein expression of cell cycle regulators (P27/CDKN1B, CCNE1, CCND1, CDK2, CDK4, CDK6).

Main Results:

  • Somatic USP8 mutations were found in 31.3% of patients.
  • USP8 mutations were associated with larger tumor size (p=0.04).
  • No significant differences in clinical features or cell cycle regulator expression were observed based on USP8 mutation status.

Conclusions:

  • USP8 mutations in corticotroph adenomas are associated with increased tumor size.
  • The hypothesis that USP8 mutations directly cause P27 underexpression and cell cycle dysregulation was not supported by this data.
  • Alternative pathways may mediate the effect of mutated USP8 on tumor growth.

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