HETEROGENEITY FOR ALLELIC LOSS IN HUMAN BREAST-CANCER

Background: Loss of heterozygosity (LOH) at specific chromosomal regio ns in the tumor cells implicates the presence of tumor suppressor gene s. However, it is also possible for an LOH to be randomly acquired and irrelevant to tumor development. Purpose: To determine whether a part icular LOH in human breast carcinomas represents a loss of tumor suppr essor gene or merely a random loss, we analyzed untreated primary brea st cancers for LOH. Methods: Ninety-eight primary human breast cancers from previously untreated patients were analyzed for LOH at 12 chromo somal regions including five randomly selected regions and seven regio ns previously reported in other cancer types and/or breast cancers. Re sults: The baseline incidence of LOH was five out of 124 tests (4%) us ing randomly selected probes on chromosomes 1p, 2p, 4p, 11q, and Xq. I ncidences of LOH significantly greater than background were seen in th e following chromosomal regions: 22q (10 of 26 cases, 38%); 18p (five of 24 cases, 21%); 17p (30 of 59 cases, 51%); 13q (five of 14 cases, 3 6 %); 3p (13 of 28 cases, 46%); and 1q (18 of 70 cases, 26%). In contr ast to previous reports, the incidence of LOH was not significantly di fferent from background for 11p15. In all cases, results were the same for metastatic lymph nodes and primary tumors, suggesting that the lo sses occurred early in the malignant progression. In cases with LOH at more than one locus, the same DNA sample often varied in degree of si gnal reduction for the missing alleles. Conclusion: These observations indicate the presence of both intertumor and intratumor heterogeneity for LOH.