Detection of allelic losses on 17q12-q21 chromosomal region in benign lesions and malignant tumors occurring in a familial context.

ABSTRACT

A predisposing gene (BRCA-1) for breast and ovarian cancer has been located on chromosomal region 17q12-21. According to Knudson's hypothesis if this gene is a tumor suppressor gene, allelic losses would be found in tumors occurring in families with cancer aggregations. We studied 25 samples of both benign lesions and malignant tumors, from breast cancer site-specific families and other familial cancer aggregations. Allelic losses seem to be more frequent in tumors from breast site-specific families but also include the predisposing locus in other syndromes, suggesting a role of BRCA-1 in such families. Finding of allele losses near this locus in benign lesions suggests that such alterations may represent a first step in breast carcinogenesis. It is noteworthy that allele losses involve larger chromosome fragments in malignant tumors than in benign lesions where BRCA-1 is not lost, suggesting a similar mechanism for genomic deletion in the tumorigenesis of the colon and of the breast.