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Clonality studies of benign proliferative breast lesions from breast cancer patients

Journal Article · · American Journal of Human Genetics
OSTI ID:133551
; ;  [1]
  1. Univ. of Texas Health Science Center, San Antonio, TX (United States); and others

We are examining patients with concurrent benign proliferative breast disease, in situ and/or invasive breast cancer. Epidemiological data indicates that these morphologically defined lesions may be categorized as those with little malignant potential (e.g., typical hyperplasia or proliferative disease without atypia (PDWA)), those with significant malignant potential which may already be {open_quotes}initiated{close_quotes} (e.g., atypical ductal hyperplasia (ADH)), and {open_quotes}transformed{close_quotes} lesions which are malignant but not yet invasive (e.g., ductal carcinoma in situ (DCIS)). Our studies concern genetic analysis of clonality to determine whether or not these morphologically defined lesions represent sequential evolutionary stages in the ontogeny of invasive breast cancer. Loss-of-heterozygosity (LOH) analysis is with highly polymorphic simple sequence repeat polymorphisms is used to identify clonal neoplasms and LOHs shared between concurrent lesions is interpreted as evidence of clonal evolution. Seventy-five sets of concurrent breast lesions have been examined to date. Approximately 80% of the benign proliferative lesions demonstrate at least one LOH, indicating that the majority of benign proliferative breast lesions from women with breast cancer are clonal neoplasms. To examine whether the concurrent breast proliferative lesion are clonally related, the patterns of LOH detected in a set of concurrent lesions was examined. We estimate that approximately 50% of the PDWAs and ADH lesions and 65% of the DCIS lesions shared their LOH patterns with more advanced lesions in the same breast. These results support the notion that a precursor/product relationship may exist between these lesions and the cancers they accompany.

OSTI ID:
133551
Report Number(s):
CONF-941009--
Journal Information:
American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
Country of Publication:
United States
Language:
English

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