Genome chaos: Survival strategy during crisis

Guo Liu, Joshua B. Stevens, Steven D. Horne, Batoul Y. Abdallah, Karen J. Ye, Steven W. Bremer, Christine J. Ye, David J. Chen, Henry H. Heng

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)528-537
Number of pages10
JournalCell Cycle
Volume13
Issue number4
DOIs
StatePublished - Feb 15 2014

Fingerprint

Genome
Neoplasms
Cytogenetic Analysis
Neoplasm Genes
Karyotype
Transcriptome
Chromosomes

Keywords

  • Cancer evolution
  • Chromoplexy
  • Chromosome fragmentation
  • Chromothripsis
  • Genome chaos
  • Genome theory
  • Karyotypic chaos
  • Macro-cellular evolution
  • System inheritance

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Liu, G., Stevens, J. B., Horne, S. D., Abdallah, B. Y., Ye, K. J., Bremer, S. W., ... Heng, H. H. (2014). Genome chaos: Survival strategy during crisis. Cell Cycle, 13(4), 528-537. https://doi.org/10.4161/cc.27378

Genome chaos : Survival strategy during crisis. / Liu, Guo; Stevens, Joshua B.; Horne, Steven D.; Abdallah, Batoul Y.; Ye, Karen J.; Bremer, Steven W.; Ye, Christine J.; Chen, David J.; Heng, Henry H.

In: Cell Cycle, Vol. 13, No. 4, 15.02.2014, p. 528-537.

Research output: Contribution to journalArticle

Liu, G, Stevens, JB, Horne, SD, Abdallah, BY, Ye, KJ, Bremer, SW, Ye, CJ, Chen, DJ & Heng, HH 2014, 'Genome chaos: Survival strategy during crisis', Cell Cycle, vol. 13, no. 4, pp. 528-537. https://doi.org/10.4161/cc.27378
Liu G, Stevens JB, Horne SD, Abdallah BY, Ye KJ, Bremer SW et al. Genome chaos: Survival strategy during crisis. Cell Cycle. 2014 Feb 15;13(4):528-537. https://doi.org/10.4161/cc.27378
Liu, Guo ; Stevens, Joshua B. ; Horne, Steven D. ; Abdallah, Batoul Y. ; Ye, Karen J. ; Bremer, Steven W. ; Ye, Christine J. ; Chen, David J. ; Heng, Henry H. / Genome chaos : Survival strategy during crisis. In: Cell Cycle. 2014 ; Vol. 13, No. 4. pp. 528-537.
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