Multiple regions of chromosome 4 demonstrating allelic losses in breast carcinomas

Allelotyping studies suggest that allelic losses at one or both arms of chr omosome 4 are frequent in several tumor types, but information about breast cancer is scant. A recent comparative genomic hybridization analysis revea led frequent losses of chromosome 4 in breast carcinomas. In an effort to m ore precisely locate the putative tumor suppressor gene(s) on chromosome 4 involved in the pathogenesis of breast carcinomas, we performed loss of het erozygosity studies using 19 polymorphic microsatellite markers. After prec ise microdissection of archival surgical cases, we analyzed DNA obtained fr om 44 breast carcinomas for loss of heterozygosity, In addition, DNA from t umor cell lines derived from 14 of these 44 breast carcinomas were also ana lyzed, We observed deletions of chromosome 4 at multiple sites in both tumo r cell lines and breast carcinomas, The deletions in cell lines and their c orresponding tumors were extensive in nature, whereas they were more locali zed in noncultured breast carcinomas. The localized deletions in the noncul tured breast carcinomas clearly defined four nonoverlapping regions of freq uent deletions: 4q33-34 (76%); 4q25-26 (63%); 4p15.1-15.3 (57%); and 4p16.3 (50%), Our results suggest that there may be multiple putative tumor suppr essor genes, located on both arms of chromosome 4, whose inactivation is im portant in the pathogenesis of breast cancer.