Nature Genetics
37, 899 - 905 (2005)
Published online: 10 July 2005; | doi:10.1038/ng1596
Distinct epigenetic changes in the stromal cells of breast cancersMin Hu1, 2, Jun Yao1, 2, Li Cai3, Kurt E Bachman4, Frédéric van den Brûle5, Victor Velculescu6
& Kornelia Polyak1, 21
Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA. 2
Harvard Medical School, Boston, Massachusetts 02115, USA. 3
Research Computing, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA. 4
University of Maryland, Greenebaum Cancer Center, Baltimore, Maryland 21201, USA. 5
Laboratory of Biology and Developmental Biology, University of Liège, Sart Tilman, B-4000 Liège, Belgium. 6
Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore, Maryland 21231, USA.
Correspondence should be addressed to Kornelia Polyak Kornelia_Polyak@dfci.harvard.edu Increasing evidence suggests that changes in the cellular microenvironment contribute to tumorigenesis, but the molecular basis of these alterations is not well understood. Although epigenetic modifications of the neoplastic cells in tumors have been firmly implicated in tumorigenesis1, it is not known whether epigenetic modifications occur in the non-neoplastic stromal cells. To address this question in an unbiased and genome-wide manner, we developed a new method, methylation-specific digital karyotyping, and applied it to epithelial and myoepithelial cells, stromal fibroblasts from normal breast tissue, and in situ and invasive breast carcinomas. Our analyses showed that distinct epigenetic alterations occur in all three cell types during breast tumorigenesis in a tumor stage− and cell type−specific manner, suggesting that epigenetic changes have a role in the maintenance of the abnormal cellular microenvironment in breast cancer.
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