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The analysis of the origin of chromothripsis, catastrophic chromosomal rearrangements, has provided exceptional insights into various aspects of tumor progression and genetic disorders. Findings in chromothripsis have not only enhanced our understanding of genomic instability mechanisms, but also reshaped our views on chromosome mechanics. To date, the major mechanisms of chromothripsis described involve the incorporation of micronuclei into the primary nucleus and telomere crisis through the formation of dicentric chromosomes. Here, we reevaluated the impact of telomere and centromere sequences in the formation of micronuclei and anaphase bridges in cancer patients using our high throughput technique for the detection of telomere and centromere dysfunction and chromosomal instability biomarkers. We also discuss the emerging potential of exploiting telomere and centromere dysfunction combined with DNA damage as prognostic biomarkers and tools for personalized patient management.

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DNA Damage, Telomere and Centromere Dysfunction in Chromothripsis Rearrangements

  • 实验方案

  • 发表日期：

    2025年

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  • Radhia M’kacher,
  • Bruno Colicchio,
  • Steffen Junker,
  • Simon Schabat,
  • Raja Belaiba,
  • Louis Sontos,
  • Leonhard Heidingsfelder,
  • Wala Najar,
  • Andreas Plesch,
  • Philippe Voisin,
  • Alain Dieterlen,
  • Eric Jeandidier,
  • Patrice Carde

摘要

The analysis of the origin of chromothripsis, catastrophic chromosomal rearrangements, has provided exceptional insights into various aspects of tumor progression and genetic disorders. Findings in chromothripsis have not only enhanced our understanding of genomic instability mechanisms, but also reshaped our views on chromosome mechanics. To date, the major mechanisms of chromothripsis described involve the incorporation of micronuclei into the primary nucleus and telomere crisis through the formation of dicentric chromosomes. Here, we reevaluated the impact of telomere and centromere sequences in the formation of micronuclei and anaphase bridges in cancer patients using our high throughput technique for the detection of telomere and centromere dysfunction and chromosomal instability biomarkers. We also discuss the emerging potential of exploiting telomere and centromere dysfunction combined with DNA damage as prognostic biomarkers and tools for personalized patient management.