Loss of heterozygosity at 3p in benign lesions preceding invasive breast cancer

David M. Euhus, Anirban Maitra, Ignacio I. Wistuba, Arland Alberts, Jorge Albores-Saavedra, Adi F. Gazdar

Research output: Contribution to journalArticle

Abstract

Background. Loss of heterozygosity (LOH) at chromosome 3p is one of the most common genetic abnormalities identified in human cancers and has occasionally been noted in benign proliferative lesions predisposing to breast cancer. If the frequency of LOH at 3p in benign proliferative lesions correlates with the subsequent development of breast cancer, it may be possible to develop powerful tools for molecular risk assessment based on this technology. Materials and methods. Archival paraffin-embedded tissues from benign breast biopsies in five women who have developed breast cancer and three women who have not developed breast cancer were microdissected and allelotyped at 3p using six microsatellite markers. Results. No LOH was detected in the biopsies from women who have not developed breast cancer. For women developing breast cancer, the proportion of informative loci showing LOH in the benign proliferative lesions was 0.47 as compared to 0.57 for the associated breast cancers. There was no LOH detected in epithelial DNA from a fibroadenoma. Of 15 informative loci, 4 (27%) showed LOH in both the benign proliferative lesion and the associated cancer; however, the actual parental allele lost was different in three of these four cases. Conclusions. These results suggest that there are specific patterns of genetic instability common to preneoplastic lesions and the breast cancers that subsequently develop even when the paired lesions are not clonally related. LOH analysis of benign breast epithelium may provide a tool for molecular risk assessment and a surrogate endpoint for breast cancer chemoprevention trials.

Original languageEnglish (US)
Pages (from-to)13-18
Number of pages6
JournalJournal of Surgical Research
Volume83
Issue number1
DOIs
StatePublished - May 1 1999
Externally publishedYes

Keywords

  • 3p
  • Benign breast lesions
  • Breast cancer
  • Loss of heterozygosity
  • Polymerase chain reaction

ASJC Scopus subject areas

  • Surgery

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  • Cite this

    Euhus, D. M., Maitra, A., Wistuba, I. I., Alberts, A., Albores-Saavedra, J., & Gazdar, A. F. (1999). Loss of heterozygosity at 3p in benign lesions preceding invasive breast cancer. Journal of Surgical Research, 83(1), 13-18. https://doi.org/10.1006/jsre.1998.5549