Genome chaos: Survival strategy during crisis

Genome chaos, a process of complex, rapid genome re-organization, results in the formation of chaotic genomes, which is followed by the potential to establish stable genomes. It was initially detected through cytogenetic analyses, and recently confirmed by whole-genome sequencing efforts which ident...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2014-02, Vol.13 (4), p.528-537
Main Authors: Liu, Guo, Stevens, Joshua, Horne, Steven, Abdallah, Batoul, Ye, Karen, Bremer, Steven, Ye, Christine, Chen, David J., Heng, Henry
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
cancer evolution
Cell Line, Tumor
Cell Survival - genetics
chromoplexy
Chromosomal Instability
Chromosome Aberrations
chromosome fragmentation
chromothripsis
DNA Damage
DNA End-Joining Repair
Doxorubicin - pharmacology
Genome
genome chaos
genome theory
Humans
Karyotype
karyotypic chaos
macro-cellular evolution
Mice
Mitomycin - pharmacology
system inheritance
Transcriptome
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Summary:Genome chaos, a process of complex, rapid genome re-organization, results in the formation of chaotic genomes, which is followed by the potential to establish stable genomes. It was initially detected through cytogenetic analyses, and recently confirmed by whole-genome sequencing efforts which identified multiple subtypes including "chromothripsis", "chromoplexy", "chromoanasynthesis", and "chromoanagenesis". Although genome chaos occurs commonly in tumors, both the mechanism and detailed aspects of the process are unknown due to the inability of observing its evolution over time in clinical samples. Here, an experimental system to monitor the evolutionary process of genome chaos was developed to elucidate its mechanisms. Genome chaos occurs following exposure to chemotherapeutics with different mechanisms, which act collectively as stressors. Characterization of the karyotype and its dynamic changes prior to, during, and after induction of genome chaos demonstrates that chromosome fragmentation (C-Frag) occurs just prior to chaotic genome formation. Chaotic genomes seem to form by random rejoining of chromosomal fragments, in part through non-homologous end joining (NHEJ). Stress induced genome chaos results in increased karyotypic heterogeneity. Such increased evolutionary potential is demonstrated by the identification of increased transcriptome dynamics associated with high levels of karyotypic variance. In contrast to impacting on a limited number of cancer genes, re-organized genomes lead to new system dynamics essential for cancer evolution. Genome chaos acts as a mechanism of rapid, adaptive, genome-based evolution that plays an essential role in promoting rapid macroevolution of new genome-defined systems during crisis, which may explain some unwanted consequences of cancer treatment.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.27378