DETECTION OF ALLELIC LOSSES ON 17Q12-Q21 CHROMOSOMAL REGION IN BENIGNLESIONS AND MALIGNANT-TUMORS OCCURRING IN A FAMILIAL CONTEXT

A predisposing gene (BRCA-1) for breast and ovarian cancer has been lo cated on chromosomal region 17q12-21. According to Knudson's hypothesi s if this gene is a tumor suppressor gene, allelic losses would be fou nd in tumors occurring in families with cancer aggregations. We studie d 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-spe cific families but also include the predisposing locus in other syndro mes, suggesting a role of BRCA-1 in such families. Finding of allele l osses 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 t umors than in benign lesions where BRCA-1 is not lost, suggesting a si milar mechanism for genomic deletion in the tumorigenesis of the colon and of the breast.