USP8 Mutations and Cell Cycle Regulation in Corticotroph Adenomas
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 Cushingʼs disease and to elucidate the relationsh...
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Published in | Hormone and metabolic research Vol. 52; no. 2; pp. 117 - 123 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Stuttgart · New York
Georg Thieme Verlag KG
01.02.2020
|
Subjects | |
Online Access | Get full text |
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Summary: | 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 Cushingʼs disease and to elucidate the
relationship between
USP8
mutations and P27 underexpression in these
tumors. Retrospective study with 32 patients with Cushingʼs disease was
followed at the Ribeirao Preto Medical School University Hospital. We
evaluated the patientsʼ 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. |
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ISSN: | 0018-5043 1439-4286 |
DOI: | 10.1055/a-1089-7806 |