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Methylation of p16(INK4a) promoters occurs in vivo in histologically normal human mammary epitheliaCultures of human mammary epithelial cells (HMECs) contain a subpopulation of variant cells with the capacity to propagate beyond an in vitro proliferation barrier. These variant HMECs, which contain hypermethylated and silenced p16(INK4a) (p16) promoters, eventually accumulate multiple chromosomal changes, many of which are similar to those detected in premalignant and malignant lesions of breast cancer. To determine the origin of these variant HMECs in culture, we used Luria-Delbruck fluctuation analysis and found that variant HMECs exist within the population before the proliferation barrier, thereby raising the possibility that variant HMECs exist in vivo before cultivation. To test this hypothesis, we examined mammary tissue from normal women for evidence of p16 promoter hypermethylation. Here we show that epithelial cells with methylation of p16 promoter sequences occur in focal patches of histologically normal mammary tissue of a substantial fraction of healthy, cancer-free women.
Document ID
20040087764
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Holst, Charles R.
(Department of Pathology and University of California at San Francisco Comprehensive Cancer Center 94143-0511 United States)
Nuovo, Gerard J.
Esteller, Manel
Chew, Karen
Baylin, Stephen B.
Herman, James G.
Tlsty, Thea D.
Date Acquired
August 21, 2013
Publication Date
April 1, 2003
Publication Information
Publication: Cancer research
Volume: 63
Issue: 7
ISSN: 0008-5472
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: CA73952
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center

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