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2011 ; 34
(1-2
): 21-33
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Nuclear position and shape deformation of chromosome 8 territories in pancreatic
ductal adenocarcinoma
#MMPMID21483101
Timme S
; Schmitt E
; Stein S
; Schwarz-Finsterle J
; Wagner J
; Walch A
; Werner M
; Hausmann M
; Wiech T
Anal Cell Pathol (Amst)
2011[]; 34
(1-2
): 21-33
PMID21483101
show ga
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.