Long Interspersed Nuclear Element 1 Retrotransposons Become Deregulated during the Development of Ovarian Cancer Precursor Lesions.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
24
08
2018
revised:
20
10
2018
accepted:
19
11
2018
pubmed:
17
12
2018
medline:
13
11
2019
entrez:
17
12
2018
Statut:
ppublish
Résumé
There is growing evidence that most high-grade serous ovarian carcinomas likely arise from local dissemination of precursor lesions of the fallopian tube. Evolution of these lesions from early p53 signatures to latter-stage, serous tubal intraepithelial carcinomas (STICs) is characterized by cytologic atypia, accumulation of somatic mutations, and genomic instability, the etiologies of which remain unclear. Long interspersed element 1 (LINE-1) retrotransposon is expressed in many carcinomas, including high-grade serous ovarian carcinoma, where it contributes to genomic instability; however, the timing of LINE-1 activation during this evolution has yet to be elucidated. In this study, we assessed LINE-1 open reading frame 1 protein expression in 12 p53 signature lesions, 32 STICs, and 112 various types of ovarian cancers via immunohistochemical staining and examined LINE-1 promoter methylation in representative cases. We found that 78% and 57% of STICs, with and without concurrent ovarian carcinomas, respectively, exhibited intense LINE-1 immunoreactivity compared with adjacent, normal-appearing fallopian tube epithelium. Hypomethylation of the LINE-1 promoter was found in all STICs exhibiting overexpression. None of the 12 p53 signatures demonstrated significant LINE-1 expression. In ovarian cancer, 84 (75%) of 112 ovarian carcinomas overexpressed LINE-1. Our results indicate that LINE-1 retrotransposons often become deregulated during progression of ovarian cancer precursor lesions from the p53 signature to STIC stages and remain highly expressed in carcinoma.
Identifiants
pubmed: 30553834
pii: S0002-9440(18)30690-4
doi: 10.1016/j.ajpath.2018.11.005
pmc: PMC6412403
pii:
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
513-520Subventions
Organisme : NCI NIH HHS
ID : U01 CA200469
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124531
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA228991
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM107632
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215483
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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