SUBLOCALIZATION OF SMALLEST COMMON REGIONS OF DELETION ON CHROMOSOME 17Q12-Q23 IN SPORADIC PRIMARY BREAST-TUMORS

Frequent loss of heterozygosity (LOH) on the long arm of chromosome 17 has been described in breast tumor DNAs by a number of groups, and re cent fine genetic mapping and cloning of an inherited breast-ovarian c ancer susceptibility locus (BRCA1) to a small region of 17q12-q21 has focused interest on this area. The absence of sporadic mutations in th e BRCA1 gene in breast tumors studied so far suggests that there may b e other tumor suppressor genes in the region involved in sporadic brea st cancer. We studied 28 sporadic breast cancers with 14 highly polymo rphic markers on chromosome 17 (2 on 17p and 12 on 17q). Most of the 1 7q markers are located within the 17q12-q23 region. We confirmed that 50% of tumors have deletions of at least one locus on chromosome arm 1 7q, and that half the deleted cases probably correspond to monosomies 17 or 17q. The other half correspond to a partial deletion on 17q and were used to identify 2 smallest common deleted regions (SCDR1 and SCD R2) on 17q12-q23. SCDR1 comprised the THRA1 gene, but not the 2 flanki ng loci tested (D17S250 and D17S800); while SCDR2 was defined by loci GIP and GH. BRCA1 was deleted in half the cases but it is outside the SCDR1. Moreover, breast tumors in young women frequently showed chromo some 17 alterations.