Long Interspersed Nuclear Element 1 Retrotransposons Become Deregulated during the Development of Ovarian Cancer Precursor Lesions

Thomas R. Pisanic, Shiho Asaka, Shiou Fu Lin, Ting Tai Yen, Hanru Sun, Asli Bahadirli-Talbott, Tza Huei Wang, Kathleen Burns, Tian-Li Wang, Ie Ming Shih

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)513-520
Number of pages8
JournalAmerican Journal of Pathology
Volume189
Issue number3
DOIs
StatePublished - Mar 1 2019

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Retroelements
Ovarian Neoplasms
Carcinoma in Situ
Carcinoma
Fallopian Tubes
Genomic Instability
Methylation
Open Reading Frames
Epithelium
Staining and Labeling
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Long Interspersed Nuclear Element 1 Retrotransposons Become Deregulated during the Development of Ovarian Cancer Precursor Lesions. / Pisanic, Thomas R.; Asaka, Shiho; Lin, Shiou Fu; Yen, Ting Tai; Sun, Hanru; Bahadirli-Talbott, Asli; Wang, Tza Huei; Burns, Kathleen; Wang, Tian-Li; Shih, Ie Ming.

In: American Journal of Pathology, Vol. 189, No. 3, 01.03.2019, p. 513-520.

Research output: Contribution to journalArticle

Pisanic, Thomas R. ; Asaka, Shiho ; Lin, Shiou Fu ; Yen, Ting Tai ; Sun, Hanru ; Bahadirli-Talbott, Asli ; Wang, Tza Huei ; Burns, Kathleen ; Wang, Tian-Li ; Shih, Ie Ming. / Long Interspersed Nuclear Element 1 Retrotransposons Become Deregulated during the Development of Ovarian Cancer Precursor Lesions. In: American Journal of Pathology. 2019 ; Vol. 189, No. 3. pp. 513-520.
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