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Contiguous Patches of Normal Human Mammary Epithelium Derived from a Single Stem Cell: Implications for Breast Carcinogenesis¹

University of Southern California/Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, California 90033-4526 [Y. C. T., P. W. N., P. A. J.], and Geraldine Brush Cancer Research Institute, California Pacific Medical Center, San Francisco, California 94115-1932 [Y. L., G. Z., H. S. S.]

Tissue clonality can be assessed in females by analyzing the methylation status of polymorphic DNA markers on X-linked genes because extensive de novo methylation of one allele at the preimplantation stage is associated with its permanent inactivation. We applied X chromosome inactivation toward understanding human breast morphogenesis by examining the nonmalignant breast epithelium from two reduction mammaplasties and a mastectomy. We found that entire lobules and large ducts of normal breast tissue have the same X chromosome inactivated, suggesting that they are derived from the same stem cell. The regions of inactivation of a particular X chromosome do not extend over an entire breast, so that ducts and lobules with opposite chromosomes inactivated are present within a single breast. Potential relevance of these observations for malignant transformation is discussed.

¹ This work was supported by National Cancer Institute SPORE Grant 1P59CA58207 and National Cancer Institute Grant R35 CA49758.

² To whom requests for reprints should be addressed, at Geraldine Brush Cancer Research Institute, California Pacific Medical Center, 2330 Clay Street, Room 201, San Francisco, CA 94115-1932.

Received 4/ 6/95. Accepted 11/ 8/95.

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