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Title: The 3D nuclear organization of telomeres during endometrial carcinoma development
Authors: Danescu, Adrian
Supervisor: Hombach-Klonisch, Sabine (Human Anatomy and Cell Science)
Examining Committee: Simard, Louise (Biochemistry and Medical Genetics) Mai, Sabine (Biochemistry & Medical Genetics) Scott, J. Elliott (Oral Biology)
Graduation Date: May 2012
Keywords: endometrial cancer
3D telomere profile
telomere fluorescence in-situ hybridization (telomere-FISH)
nucelar architecture
Issue Date: 4-Apr-2012
Abstract: Early diagnosis of endometrial cancer (EC) is uncertain and women undergo preventive hysterectomy in cases where a non-invasive treatment can be used instead. To contribute to solving this challenge we investigated if early changes in the nuclear 3D telomere architecture during carcinoma development can be detected prior to the first morphological evidence of precancerous lesions. We utilized Pten heterozygous mice that develop progressive carcinoma in the endometrial tissue similar to EC development in women. We used telomere fluorescence in situ hybridization (FISH), 3D molecular imaging and analysis techniques on interphase nuclei of endometrial glandular epithelial cells to identify alterations in the 3D-telomere profile. We found that telomere dysfunction in Pten heterozygous mice is present already in endometrial simple hyperplasia lesions prior to detectable loss of PTEN protein expression and that the 3D telomere architecture has a specific signature that indicates early telomere dysfunction predictive for endometrial malignant transformation.
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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