Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity
David Gisselsson,Louise Pettersson,Mattias Höglund,Markus Heidenblad,Ludmila Gorunova,Joop Wiegant,Fredrik Mertens,Paola Dal Cin,Felix Mitelman,Nils Mandahl +9 more
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Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells, suggesting 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.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.read more
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References
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Journal Article
An international system for human cytogenetic nomenclature
TL;DR: An exceptional reading e-book entitled International System For Human Cytogenetic Nomenclature provides a thorough legal analysis and guidance to state authorities, human rights and humanitarian actors and others.
Journal ArticleDOI
The clonal evolution of tumor cell populations
TL;DR: Each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment, which should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
Journal ArticleDOI
Genetic instabilities in human cancers
TL;DR: There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
Journal Article
Participation of p53 Protein in the Cellular Response to DNA Damage
TL;DR: A role for the wild-type p53 protein in the inhibition of DNA synthesis that follows DNA damage is suggested and a new mechanism for how the loss of wild- type p53 might contribute to tumorigenesis is suggested.
Journal ArticleDOI
Requirement for p53 and p21 to Sustain G2 Arrest After DNA Damage
Fred Bunz,A. Dutriaux,Christoph Lengauer,Todd Waldman,Shibin Zhou,J. P. Brown,John M. Sedivy,Kenneth W. Kinzler,Bert Vogelstein +8 more
TL;DR: After DNA damage, many cells appear to enter a sustained arrest in the G2 phase of the cell cycle but this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21.