Oncogenes create a unique landscape of fragile sites

Recurrent genomic instability in cancer is attributed to positive selection and/or the sensitivity of specific genomic regions to breakage. Among these regions are fragile sites (FSs), genomic regions sensitive to replication stress conditions induced by the DNA polymerase inhibitor aphidicolin. How...

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Bibliographic Details
Published in:Nature communications 2015-05, Vol.6 (1), p.7094-7094, Article 7094
Main Authors: Miron, Karin, Golan-Lev, Tamar, Dvir, Raz, Ben-David, Eyal, Kerem, Batsheva
Format: Article
Language:English
Subjects:
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Cell Line, Tumor
Chromosome Fragile Sites - genetics
Chromosome Fragile Sites - physiology
Chromosome Fragility - genetics
Chromosome Fragility - physiology
Fibroblasts - physiology
Gene Deletion
Gene Expression Regulation - physiology
Genomic Instability
Humanities and Social Sciences
Humans
multidisciplinary
Multigene Family
Oncogenes - genetics
Oncogenes - physiology
Plasmids
Science
Science (multidisciplinary)
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Summary:Recurrent genomic instability in cancer is attributed to positive selection and/or the sensitivity of specific genomic regions to breakage. Among these regions are fragile sites (FSs), genomic regions sensitive to replication stress conditions induced by the DNA polymerase inhibitor aphidicolin. However, the basis for the majority of cancer genomic instability hotspots remains unclear. Aberrant oncogene expression induces replication stress, leading to DNA breaks and genomic instability. Here we map the cytogenetic locations of oncogene-induced FSs and show that in the same cells, each oncogene creates a unique fragility landscape that only partially overlaps with aphidicolin-induced FSs. Oncogene-induced FSs colocalize with cancer breakpoints and large genes, similar to aphidicolin-induced FSs. The observed plasticity in the fragility landscape of the same cell type following oncogene expression highlights an additional level of complexity in the molecular basis for recurrent fragility in cancer. Aberrant oncogene expression can cause replication stress leading to chromosomal breaks. Here the authors map the chromosomal break loci induced by two different oncogenes and by a replication inhibitor, and show that each treatment induces a unique pattern of breaks in the same cell type.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms8094