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The disappearing Barr body in breast and ovarian cancers

Nature Reviews Cancer volume 7, pages 628–633 (2007)Cite this article

Abstract

Interest has recently reawakened in whether loss of the heterochromatic X chromosome (Barr body) is prevalent in certain breast and ovarian cancers, and new insights into the mechanisms involved have emerged. Mitotic segregation errors commonly explain the loss of the inactive X chromosome (Xi), but compromise of Xi heterochromatin in some cancers may signal broader deficits of nuclear heterochromatin. The debated link between BRCA1 and Xi might reflect a general relationship between BRCA1 and heterochromatin, which could connect BRCA1 to both epigenetic and genetic instability. We suggest that heterochromatic instability is a common but largely unexplored mechanism, leading to widespread genomic misregulation and the evolution of some cancers.

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Figure 1: Three possible mechanisms that lead to the overexpression of X-linked genes in cancer.
Figure 2: Defects in XIST RNA and X inactivation might reflect a broader compromise of the heterochromatic compartment.
Figure 3: BRCA1 associates with heterochromatic structures.

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Acknowledgements

The authors are funded by grants from the US National Institutes of Health and a Department of Defense predoctoral research fellowship (G.J.P.).

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Authors and Affiliations

  1. Lisa L. Hall and Jeanne B. Lawrence are at the Department of Cell Biology, Gayle J. Pageau, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.,

    Gayle J. Pageau, Lisa L. Hall & Jeanne B. Lawrence

  2. Shridar Ganesan is at the Department of Medicine, Cancer Institute of New Jersey, Cancer Genomics and Molecular Oncology, UMDNJ-Robert Wood Johnson School of Medicine, New Brunswick, New Jersey 08093, USA.,

    Shridar Ganesan

  3. David M. Livingston is at the Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.,

    David M. Livingston

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  1. Gayle J. Pageau
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Correspondence to David M. Livingston or Jeanne B. Lawrence.

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Pageau, G., Hall, L., Ganesan, S. et al. The disappearing Barr body in breast and ovarian cancers. Nat Rev Cancer 7, 628–633 (2007). https://doi.org/10.1038/nrc2172

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