LOCALIZATION OF A BREAST-CANCER TUMOR-SUPPRESSOR GENE TO A 3-CM INTERVAL WITHIN CHROMOSOMAL REGION 16Q22

Allelic losses on chromosome 16q in tumour cells are frequent in a var iety of malignancies, suggesting the presence of one or more tumour-su ppressor genes in the region. Among 210 sporadic breast cancers we exa mined using 15 microsatellite markers on the long arm of chromosome 16 , heterozygosity for at least one locus was lost in 141 (67%). Detaile d deletion mapping revealed two distinct commonly deleted regions. One region was defined as a 3-cM interval flanked by markers D16S512 and D16S515 at 16q22; the second consisted of a 9.5-cM interval flanked by markers D16S498 and D16S303 at q24.3. Allelic loss on 16q was observe d frequently in small tumours, tumours without lymph node metastasis a nd tumours of the non-invasive histological type as well as in tumours of more advanced phenotype, suggesting that inactivation of one of at least two tumour-suppressor genes on 16q plays a role in early stage breast carcinogenesis.