The loss of heterozygosity (LOH) The genetic etiology of breast cancer appears, at least in part, to reflect an accumulation of mutations that are selected during tumor development. These mutations are thought to deregulate normal development of the mammary gland or to provide the affected cell with a selective growth advantage in the host (1-5). In breast cancer the most frequent type of tumor-associated mutation is the somatic loss of heterozygosity (LOH) at specific regions of the human genome (6).

We have constructed a physical map of a 4 cM region on chromosome 17q12-21 that contains the hereditary breast and ovarian cancer gene BRCA1. The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones, onto which we have placed 112 PCR markers. We have localized more than 20 genes on this map, ten of which had not been mapped to the region previously, and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes. Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations. These new reagents should facilitate the identification of BRCA1.

A systematic study of primay human breast tumor DNA demonstrated that three proto‐oncogenes or regions of the genome c‐myc, int‐2, and c‐erbB2) are frequently amplified and that there is loss of heterozygosity (LOH) on chromosomes 1p(37%), 1q(20%), 3p(30%), 7(41%), 11p(20%), 13q(30%), 17p(49%), 17q(29%), and 18q(34%). Specific subsets of tumors can be defined based on the particular collection of mutations they contain. For instance, LOH on chromosomes 11p, 17p, and 18q frequently occurs in the same tumor. A search for putative tumor suppressor genes within the regions of the genome affected by LOH has been started. In a comprehensive molecular analysis of the p53 gene on chromosome 17p, 46% of the tumors contained a point mutation in the p53 gene. Cancer 1992; 69:1582‐1588.

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