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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\n                    <jats:italic>in situ<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.090013497","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"5357-5362","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":360,"title":["Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity"],"prefix":"10.1073","volume":"97","author":[{"given":"David","family":"Gisselsson","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden; Laboratory for Cytochemistry and Cytometry, Department of Molecular Cell Biology, Leiden University Medical Center, 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