Three-dimensional nuclear telomere architecture changes during endometrial carcinoma development

Adrian Danescu, Sandra Herrero Gonzalez, Antonio Di Cristofano, Sabine Mai, Sabine Hombach-Klonisch

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)716-732
Number of pages17
JournalGenes Chromosomes and Cancer
Volume52
Issue number8
DOIs
StatePublished - Aug 2013

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Telomere
Endometrial Neoplasms
Hyperplasia
Epithelial Cells
Tumor Suppressor Genes
Fluorescence In Situ Hybridization
Chromosome Aberrations
Epithelium
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Three-dimensional nuclear telomere architecture changes during endometrial carcinoma development. / Danescu, Adrian; Herrero Gonzalez, Sandra; Di Cristofano, Antonio; Mai, Sabine; Hombach-Klonisch, Sabine.

In: Genes Chromosomes and Cancer, Vol. 52, No. 8, 08.2013, p. 716-732.

Research output: Contribution to journalArticle

Danescu, Adrian ; Herrero Gonzalez, Sandra ; Di Cristofano, Antonio ; Mai, Sabine ; Hombach-Klonisch, Sabine. / Three-dimensional nuclear telomere architecture changes during endometrial carcinoma development. In: Genes Chromosomes and Cancer. 2013 ; Vol. 52, No. 8. pp. 716-732.
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