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Abnormal nuclear shape in solid tumors reflects mitotic instability

Gisselsson, D LU ; Björk, J LU ; Höglund, M LU ; Mertens, F LU ; Dal Cin, P ; Akerman, M and Mandahl, N LU (2001) In American Journal of Pathology 158(1). p.199-206
Abstract

Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (<11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an... (More)

Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (<11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an osteosarcoma cell line exposed to irradiation. A linear correlation was found between the frequency of abnormalities in nuclear shape, on one hand, and cells with unstable chromosomes (r = 0.87) and anaphase bridge configurations (r = 0.98), on the other hand. The relation between nuclear shape and karyotypic pattern was investigated further in cultures from 58 tumors of bone, soft tissue, and epithelium. Blebs, strings, and micronuclei were significantly more frequent in tumors that contained rings, dicentrics, or telomeric associations than in those exhibiting only stable aberrations (P: < 0.001) and a positive correlation (r = 0.78) was found between the frequency of such nuclear abnormalities and the intratumor heterogeneity of structural chromosome aberrations. These results indicate that the formation of nuclear blebs, chromatin strings, and micronuclei in malignant tissues is closely related to the breakage-fusion-bridge type of mitotic disturbances. Abnormalities in nuclear shape may thus primarily be regarded as an indicator of genetic instability and intratumor heterogeneity, independent of cytogenetic complexity and the grade of malignancy.

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keywords
Cell Line, Cell Nucleus, Chromatin, Chromosome Aberrations, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Micronuclei, Chromosome-Defective, Mitosis, Neoplasms, Tumor Cells, Cultured, Journal Article, Research Support, Non-U.S. Gov't
in
American Journal of Pathology
volume
158
issue
1
pages
8 pages
publisher
American Society for Investigative Pathology
external identifiers
  • pmid:11141493
  • scopus:0035144955
  • pmid:11141493
ISSN
1525-2191
DOI
10.1016/S0002-9440(10)63958-2
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Occupational and Environmental Medicine (013078001), Division of Clinical Genetics (013022003), Pathology, (Lund) (013030000)
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47f4681f-0bee-41fc-9ee1-a395ff3389df (old id 1120439)
date added to LUP
2016-04-01 12:18:44
date last changed
2021-01-26 03:57:06
@article{47f4681f-0bee-41fc-9ee1-a395ff3389df,
  abstract     = {<p>Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (&lt;11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an osteosarcoma cell line exposed to irradiation. A linear correlation was found between the frequency of abnormalities in nuclear shape, on one hand, and cells with unstable chromosomes (r = 0.87) and anaphase bridge configurations (r = 0.98), on the other hand. The relation between nuclear shape and karyotypic pattern was investigated further in cultures from 58 tumors of bone, soft tissue, and epithelium. Blebs, strings, and micronuclei were significantly more frequent in tumors that contained rings, dicentrics, or telomeric associations than in those exhibiting only stable aberrations (P: &lt; 0.001) and a positive correlation (r = 0.78) was found between the frequency of such nuclear abnormalities and the intratumor heterogeneity of structural chromosome aberrations. These results indicate that the formation of nuclear blebs, chromatin strings, and micronuclei in malignant tissues is closely related to the breakage-fusion-bridge type of mitotic disturbances. Abnormalities in nuclear shape may thus primarily be regarded as an indicator of genetic instability and intratumor heterogeneity, independent of cytogenetic complexity and the grade of malignancy.</p>},
  author       = {Gisselsson, D and Björk, J and Höglund, M and Mertens, F and Dal Cin, P and Akerman, M and Mandahl, N},
  issn         = {1525-2191},
  language     = {eng},
  number       = {1},
  pages        = {199--206},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Abnormal nuclear shape in solid tumors reflects mitotic instability},
  url          = {http://dx.doi.org/10.1016/S0002-9440(10)63958-2},
  doi          = {10.1016/S0002-9440(10)63958-2},
  volume       = {158},
  year         = {2001},
}