Progression of sporadic primary breast tumors: Study of loss of heterozygosity using genetic markers spanning the BRCA1 locus on chromosome 17q

Loss of heterozygosity (LOH) often reflects the presence of a mutated gene or tumor suppressor gene on the remaining chromosome. Cytogenetic analysis of primary and metastatic breast tumors has demonstrated frequent LOH involving the long arm of chromosome 17, (17q). This locus contains a gene responsible for familial predisposition to breast cancer, termed BRCA1. Four polymorphic STR markers were chosen to span the prospective BRCA1 locus on 17q. These markers span a 30-cM interval on 17q. LOH is demonstrated in sporadic breast carcinomas, in the progressive types: intraductal, infiltrating, metastatic and recurrence. D17S579 was deleted in 44% (11 of 25), NM23 was deleted in 14% (3 of 21), THRA1 was deleted in 11% (2 of 17), and D17S183 is deleted in 40% (8 of 20) of the tumors examined. The 18 cases representing metastatic tumor showed 44% (8 of 18) LOH, Infiltrating shows 60% (18 of 30) and Intraductal showed 16% (1 of 6) of LOH. Recurrence was seen in 100% of those tested for all marker. This data supports the recent isolation of the breast cancer gene, BRCA1, which is localized to chromosome 17q21. However, this gene shows no mutation in LOH analysis for sporadic breast cancer. This indicates the possibility of other genes related to early-onset breast cancer.