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.

Author affiliations

1. Gayle J. Pageau, Lisa L. Hall and Jeanne B. Lawrence are at the Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
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.
3. David M. Livingston is at the Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Correspondence to: David M. Livingston³ Email: david_livingston@dfci.harvard.edu

Correspondence to: Jeanne B. Lawrence¹ Email: Jeanne.Lawrence@umassmed.edu

Published online 5 July 2007

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