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Monoclonality and Genetic Instability in Premalignant Breast Tissue

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Annual rept. 1 Jan 2000-1 Jan 2001

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By the time a cancer is detected, its tumor cells already exhibit myriad genetic abnormalities. To gain a better understanding of genetic events that occur early in breast carcinogenesis, this research examined genetic abnormalities 1 in histologically normal tissue from women at low, medium or high degrees of breast cancer risk, using archival specimens of reduction mammoplasties, and of diagnoses of atypical hyperplasia and breast cancers, respectively and 2 in synchronously occurring putative precursor lesions, including normal-appearing epithelium, simple and atypical proliferative hyperplastic lesions and carcinomas themselves. Each specimen is microdissected, its DNA examined using a panel of selected microsatellite markers, and evidence of clonal abnormalities sought, in particular loss of heterozygosity LOH and microsatellite instability MI. Investigation of the projects first goal generated data regarding the timing and sites of early genetic abnormalities. These data raise the possibility that a field defect exists in certain breast tissue. Investigation of the second goal is uncovering that a variety of clonal relationships exist between multiple synchronous putative precursors. These studies are identifying important sites of genetic abnormalities in early breast cancer precursors, and begin to outline a sequence of acquired genetic abnormalities needed for precursor lesions to evolve into full-blown malignancies.

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  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

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