A New Role for Hypoxia in Tumor Progression: Induction of Fragile Site Triggering Genomic Rearrangements and Formation of Complex DMs and HSRs

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