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Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity

Gisselsson Nord, David LU ; Pettersson, Louise; Höglund, Mattias LU ; Heidenblad, Markus LU ; Gorunova, Ludmila LU ; Wiegant, J; Mertens, Fredrik LU ; Dal Cin, P; Mitelman, Felix LU and Mandahl, Nils LU (2000) In Proceedings of the National Academy of Sciences 97(10). p.5357-5362
Abstract
It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetic traits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but not in tumors with tumor-specific aberrations and low variability. Fluorescence in situ hybridization analysis demonstrated that chromosomes... (More)
It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetic traits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but not in tumors with tumor-specific aberrations and low variability. Fluorescence in situ hybridization analysis demonstrated that chromosomes participating in anaphase bridge formation were involved in a significantly higher number of structural aberrations than other chromosomes. Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells. This result suggests that a combination of mitotically unstable chromosomes and an elevated tolerance to chromosomal damage leads to constant genomic reorganization in many malignancies, thereby providing a flexible genetic system for clonal evolution and progression. (Less)
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Contribution to journal
publication status
published
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in
Proceedings of the National Academy of Sciences
volume
97
issue
10
pages
5357 - 5362
publisher
National Acad Sciences
external identifiers
  • pmid:10805796
  • scopus:12944329959
ISSN
1091-6490
DOI
10.1073/pnas.090013497
language
English
LU publication?
yes
id
8e764f78-bc02-4f8a-84fb-068ece20c611 (old id 1116706)
date added to LUP
2008-07-01 15:40:50
date last changed
2017-07-09 03:29:50
@article{8e764f78-bc02-4f8a-84fb-068ece20c611,
  abstract     = {It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetic traits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but not in tumors with tumor-specific aberrations and low variability. Fluorescence in situ hybridization analysis demonstrated that chromosomes participating in anaphase bridge formation were involved in a significantly higher number of structural aberrations than other chromosomes. Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells. This result suggests that a combination of mitotically unstable chromosomes and an elevated tolerance to chromosomal damage leads to constant genomic reorganization in many malignancies, thereby providing a flexible genetic system for clonal evolution and progression.},
  author       = {Gisselsson Nord, David and Pettersson, Louise and Höglund, Mattias and Heidenblad, Markus and Gorunova, Ludmila and Wiegant, J and Mertens, Fredrik and Dal Cin, P and Mitelman, Felix and Mandahl, Nils},
  issn         = {1091-6490},
  language     = {eng},
  number       = {10},
  pages        = {5357--5362},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity},
  url          = {http://dx.doi.org/10.1073/pnas.090013497},
  volume       = {97},
  year         = {2000},
}