Three‐dimensional nuclear telomere architecture changes during endometrial carcinoma development. Issue 8 (30th April 2013)

• Record Type: Journal Article
• Authors: Danescu, Adrian; Herrero Gonzalez, Sandra; Di, Antonio; Mai, Sabine; Hombach‐Klonisch, Sabine
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 8(2013:Aug.)
• Page Start: 716
• Page End: 732
• Publication Date: 2013-04-30
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22067
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Endometrioid or type‐I endometrial carcinoma (EC) develops from hyperproliferative glandular pathologies. Inactivation of the tumor suppressor gene <italic>PTEN</italic> is frequently associated with type‐I EC. Using a previously characterized <italic>Pten</italic> heterozygous (<italic>Pten</italic>+/‐) 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 <italic>Pten</italic>+/‐ 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 <italic>Pten</italic>+/‐ 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 <italic>Pten</italic>+/‐ 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.</p> </abstract>