A CANDIDATE TUMOR-SUPPRESSOR GENE IN HUMAN BREAST CANCERS

We have isolated a candidate gene (designated Brush-1) located at 13q1 2-q13, proximal to the retinoblastoma gene (RB1). Brush-1 codes for a 4.7-kilobase mRNA expressed at high levels in normal breast epithelium but drastically reduced in 6 of 13 breast cancer cell lines. RB1 mRNA expression is at normal levels for 5 of these 6 lines suggesting a gr eater importance of Brush-1 for breast cancer Four primary breast tumo rs which showed no loss of heterozygosity in the 13q13-q14 region demo nstrated normal levels of mRNA for both Brush-1 and RB1. However, four additional primary tumors which displayed loss of heterozygosity for this region had markedly decreased levels of Brush-1 mRNA while mainta ining the normal levels for RB1. This differential loss of Brush-1 mRN A expression for both primary tumors and breast cancer cell lines is t he expected pattern for a breast tumor suppressor gene.