Contiguous patches of normal human mammary epithelium derived from a single stem cell: implications for breast carcinogenesis.
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.
University of Southern California/Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles 90033-4526, USA.
Y C
YC
Tsai
Y
Y
Lu
P W
PW
Nichols
G
G
Zlotnikov
P A
PA
Jones
H S
HS
Smith
D001483:Base Sequence; D001940:Breast / Q000033:anatomy & histology / Q000166:cytology* / Q000502:physiology; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D002999:Clone Cells; D004303:Dosage Compensation, Genetic; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D013234:Stem Cells / Q000166:cytology*