Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma

Cell type specific radial positioning of chromosome territories (CTs) and their sub-domains in the interphase seem to have functional relevance in non-neoplastic human nuclei, while much less is known about nuclear architecture in carcinoma cells and its development during tumor progression. We anal...

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Main Authors: Sylvia Timme, Eberhard Schmitt, Stefan Stein, Jutta Schwarz-Finsterle, Jenny Wagner, Axel Walch, Martin Werner, Michael Hausmann, Thorsten Wiech
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.3233/ACP-2011-0004
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author Sylvia Timme
Eberhard Schmitt
Stefan Stein
Jutta Schwarz-Finsterle
Jenny Wagner
Axel Walch
Martin Werner
Michael Hausmann
Thorsten Wiech
author_facet Sylvia Timme
Eberhard Schmitt
Stefan Stein
Jutta Schwarz-Finsterle
Jenny Wagner
Axel Walch
Martin Werner
Michael Hausmann
Thorsten Wiech
author_sort Sylvia Timme
collection DOAJ
description Cell type specific radial positioning of chromosome territories (CTs) and their sub-domains in the interphase seem to have functional relevance in non-neoplastic human nuclei, while much less is known about nuclear architecture in carcinoma cells and its development during tumor progression. We analyzed the 3D-architecture of the chromosome 8 territory (CT8) in carcinoma and corresponding non-neoplastic ductal pancreatic epithelium. Fluorescence-in-situ-hybridization (FISH) with whole chromosome painting (WCP) probes on sections from formalin-fixed, paraffin wax-embedded tissues from six patients with ductal adenocarcinoma of the pancreas was used. Radial positions and shape parameters of CT8 were analyzed by 3D-microscopy. None of the parameters showed significant inter-individual changes. CT8 was localized in the nuclear periphery in carcinoma cells and normal ductal epithelial cells. Normalized volume and surface of CT8 did not differ significantly. In contrast, the normalized roundness was significantly lower in carcinoma cells, implying an elongation of neoplastic cell nuclei. Unexpectedly, radial positioning of CT8, a dominant parameter of nuclear architecture, did not change significantly when comparing neoplastic with non-neoplastic cells. A significant deformation of CT8, however, accompanies nuclear atypia of carcinoma cells. This decreased roundness of CTs may reflect the genomic and transcriptional alterations in carcinoma.
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spelling doaj-art-6e12b6aff7ac4944b676535a6c1d174d2025-02-03T01:00:31ZengWileyAnalytical Cellular Pathology2210-71772210-71852011-01-01341-2213310.3233/ACP-2011-0004Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal AdenocarcinomaSylvia Timme0Eberhard Schmitt1Stefan Stein2Jutta Schwarz-Finsterle3Jenny Wagner4Axel Walch5Martin Werner6Michael Hausmann7Thorsten Wiech8Institute of Pathology, University Hospital Freiburg, Freiburg im Breisgau, GermanyKirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanyKirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanyKirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanyKirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanyHelmholtz Zentrum München, German Research Center for Environmental Health, Institute of Pathology, Neuherberg, GermanyInstitute of Pathology, University Hospital Freiburg, Freiburg im Breisgau, GermanyKirchhoff Institute for Physics, University of Heidelberg, Heidelberg, GermanyInstitute of Pathology, University Hospital Freiburg, Freiburg im Breisgau, GermanyCell type specific radial positioning of chromosome territories (CTs) and their sub-domains in the interphase seem to have functional relevance in non-neoplastic human nuclei, while much less is known about nuclear architecture in carcinoma cells and its development during tumor progression. We analyzed the 3D-architecture of the chromosome 8 territory (CT8) in carcinoma and corresponding non-neoplastic ductal pancreatic epithelium. Fluorescence-in-situ-hybridization (FISH) with whole chromosome painting (WCP) probes on sections from formalin-fixed, paraffin wax-embedded tissues from six patients with ductal adenocarcinoma of the pancreas was used. Radial positions and shape parameters of CT8 were analyzed by 3D-microscopy. None of the parameters showed significant inter-individual changes. CT8 was localized in the nuclear periphery in carcinoma cells and normal ductal epithelial cells. Normalized volume and surface of CT8 did not differ significantly. In contrast, the normalized roundness was significantly lower in carcinoma cells, implying an elongation of neoplastic cell nuclei. Unexpectedly, radial positioning of CT8, a dominant parameter of nuclear architecture, did not change significantly when comparing neoplastic with non-neoplastic cells. A significant deformation of CT8, however, accompanies nuclear atypia of carcinoma cells. This decreased roundness of CTs may reflect the genomic and transcriptional alterations in carcinoma.http://dx.doi.org/10.3233/ACP-2011-0004
spellingShingle Sylvia Timme
Eberhard Schmitt
Stefan Stein
Jutta Schwarz-Finsterle
Jenny Wagner
Axel Walch
Martin Werner
Michael Hausmann
Thorsten Wiech
Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma
Analytical Cellular Pathology
title Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma
title_full Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma
title_fullStr Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma
title_full_unstemmed Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma
title_short Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma
title_sort nuclear position and shape deformation of chromosome 8 territories in pancreatic ductal adenocarcinoma
url http://dx.doi.org/10.3233/ACP-2011-0004
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