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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1116706
- author
- 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
- organization
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 97
- issue
- 10
- pages
- 5357 - 5362
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:10805796
- scopus:12944329959
- pmid:10805796
- 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
- 2016-04-01 11:36:31
- date last changed
- 2022-06-01 20:44:27
@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 Academy of 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}},
doi = {{10.1073/pnas.090013497}},
volume = {{97}},
year = {{2000}},
}