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• W1902880980 abstract "Endometrioid or type‐I endometrial carcinoma (EC) develops from hyperproliferative glandular pathologies. Inactivation of the tumor suppressor gene PTEN is frequently associated with type‐I EC. Using a previously characterized Pten heterozygous ( Pten +/‐) mouse model, this study investigates the three‐dimensional (3D) telomere profiles during progression from hyperplastic lesions to EC to test the hypothesis that altered 3D telomere profiles can be detected prior to Pten loss in early hyperproliferative lesions. We used immunohistochemistry and 3D‐telomere fluorescent in‐situ hybridization to investigate Pten expression, telomere length and signal distribution, average number and spatial distribution of telomeres and formation of telomere aggregates in uterine glandular epithelial cells from wildtype and Pten +/‐ mice. Pten showed nuclear and cytoplasmic localization in WT, predominantly cytoplasmic staining in simple hyperplasia (SH) and was markedly reduced in atypical hyperplasia (AH). Telomere length in glandular epithelial cells does not shorten with age. The average number of telomeres per nucleus was not different in WT and Pten +/‐ mice indicating the lack of substantial numeric chromosome aberrations during EC development. We observed telomere aggregates in lesions of AH and EC. SH lesions in Pten +/‐ mice differed from normal glandular epithelium by an increased relative number of shorter telomeres and by a telomere signal distribution indicative of a heterogeneous cell population. Our study revealed that alterations in the nuclear 3D telomere architecture are present in early proliferative lesions of mouse uterine tissues indicative of EC development. The changes in telomere length distribution and nuclear signal distribution precede the loss of Pten. © 2013 Wiley Periodicals, Inc." @default.
• W1902880980 created "2016-06-24" @default.
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• W1902880980 creator A5076716868 @default.
• W1902880980 date "2013-04-30" @default.
• W1902880980 modified "2023-10-16" @default.
• W1902880980 title "Three-dimensional nuclear telomere architecture changes during endometrial carcinoma development" @default.
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• W1902880980 doi "https://doi.org/10.1002/gcc.22067" @default.
• W1902880980 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5675068" @default.
• W1902880980 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23630056" @default.
• W1902880980 hasPublicationYear "2013" @default.
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