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Onset of Telomere Dysfunction and Fusions in Human Ovarian Carcinoma

1
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
4
Department of Chemistry and Applied Biological Science, South Dakota School of Mines and Technology, Rapid City, SD 57701, USA
5
Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 414; https://doi.org/10.3390/cells8050414
Received: 18 December 2018 / Revised: 25 April 2019 / Accepted: 3 May 2019 / Published: 4 May 2019
(This article belongs to the Special Issue The Role of Telomere Biology in Aging and Human Disease)
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Abstract

Telomere dysfunction has been strongly implicated in the initiation of genomic instability and is suspected to be an early event in the carcinogenesis of human solid tumors. Recent findings have established the presence of telomere fusions in human breast and prostate malignancies; however, the onset of this genomic instability mechanism during progression of other solid cancers is not well understood. Herein, we explored telomere dynamics in patient-derived epithelial ovarian cancers (OC), a malignancy characterized by multiple distinct subtypes, extensive molecular heterogeneity, and widespread genomic instability. We discovered a high frequency of telomere fusions in ovarian tumor tissues; however, limited telomere fusions were detected in normal adjacent tissues or benign ovarian samples. In addition, we found relatively high levels of both telomerase activity and hTERT expression, along with anaphase bridges in tumor tissues, which were notably absent in adjacent normal ovarian tissues and benign lesions. These results suggest that telomere dysfunction may occur early in ovarian carcinogenesis and, importantly, that it may play a critical role in the initiation and progression of the disease. Recognizing telomere dysfunction as a pervasive feature of this heterogeneous malignancy may facilitate the future development of novel diagnostic tools and improved methods of disease monitoring and treatment. View Full-Text
Keywords: telomere; telomere dysfunction; ovarian carcinoma; telomerase; genomic instability telomere; telomere dysfunction; ovarian carcinoma; telomerase; genomic instability
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Huda, N.; Xu, Y.; Bates, A.M.; Rankin, D.A.; Kannan, N.; Gilley, D. Onset of Telomere Dysfunction and Fusions in Human Ovarian Carcinoma. Cells 2019, 8, 414.

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