A DEFINED CHROMOSOME 6Q FRAGMENT (AT D6S310) HARBORS A PUTATIVE TUMOR-SUPPRESSOR GENE FOR BREAST-CANCER

Recent evidence obtained by cytogenetic and molecular studies indicate s that in breast cancer chromosome 6q is often affected by genetic cha nges suggesting the existence of putative tumor suppressor genes (TSGs ). However the function of gene(s) on this chromosome in breast cancer suppession is not understood. To substantiate further the presence of breast cancer related TSGs at 60 and to define their location, we fir st performed microcell-mediated transfer of chromosome 6 to CAL51 brea st cancer cells for studying possible suppression of malignant phenoty pe and secondly, we analysed DNAs from 46 primary breast cancers for l oss of constitutive heterozygosity (LOH) using 24 polymorphic microsat ellite markers, The chromosome transfer resulted in loss of tumorigeni city and reversion of other neoplastic properties of the microcell hyb rids. Polymorphism analysis of single hybrids revealed that they harbo red only a small donor chromosome fragment defined by the marker D6S31 0 (6q23.3-q25) and flanked by D65292 and D6S311, The LOH data suggest that four tumor suppressor gene loci mapped to the central and distal portion of 6q may be independently deleted in breast cancer. One of th ese regions corresponds to the region identified by chromosome transfe r.