A new role for hypoxia in tumor progression: induction of fragile site triggering genomic rearrangements and formation of complex DMs and HSRs - Archive ouverte HAL Access content directly
Journal Articles Molecular Cell Year : 1998

A new role for hypoxia in tumor progression: induction of fragile site triggering genomic rearrangements and formation of complex DMs and HSRs

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Arnaud Coquelle
  • Function : Author
  • PersonId : 864555
Franck Toledo
  • Function : Author
  • PersonId : 980869
Anne Bieth
  • Function : Author
Michelle Debatisse
  • Function : Correspondent author
  • PersonId : 1096452

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Abstract

Genome rearrangements including gene amplification are frequent properties of tumor cells, but how they are related to the tumor microenvironment is unknown. Here, we report direct evidence for a causal relationship between hypoxia, induction of fragile sites, and gene amplification. Recently, we showed that breaks at fragile sites initiate intrachromosomal amplification. We demonstrate here that hypoxia is a potent fragile site inducer and that, like fragile sites inducing drugs, it drives fusion of double minutes (DMs) and their targeted reintegration into chromosomal fragile sites, generating homogeneously staining regions (HSRs). This pathway operates efficiently for DMs bearing different sequences, suggesting a model of hypoxia-driven formation of the HSRs containing nonsyntenic sequences frequently observed in solid tumors.

Dates and versions

inserm-03199013 , version 1 (15-04-2021)

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Arnaud Coquelle, Franck Toledo, Sabine Stern, Anne Bieth, Michelle Debatisse. A new role for hypoxia in tumor progression: induction of fragile site triggering genomic rearrangements and formation of complex DMs and HSRs. Molecular Cell, 1998, 2 (2), pp.259-265. ⟨10.1016/s1097-2765(00)80137-9⟩. ⟨inserm-03199013⟩
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