High-resolution integrated map encompassing the breast cancer loss of heterozygosity region on human chromosome 16q22.1

Loss of heterozygosity (LOH) on the long arm of human chromosome 16 is a co mmon genetic alteration observed in both invasive ductal and invasive lobul ar breast carcinomas. We have generated a high resolution integrated map en compassing the smallest region of LOH overlap within chromosome 16q22.1 (SR O2). Southern hybridization experiments using more than 140 probes resulted in the assembly of 152 bacterial large-insert clones into a 2.8-Mb contig covering SRO2. The structure of the contig was verified by long-range mappi ng using total human genomic DNA, and the contig orientation was determined by fluorescence in situ hybridization. A total of 68 transcripts have been identified in the map. One of the genes residing within SRO2 is the E-cadh erin gene, CDH1, which has previously been shown to be mutated in lobular b reast carcinomas, resulting in loss of E-cadherin expression. In most cases of ductal carcinoma, which is the major mammary cancer type, E-cadherin is normally expressed, suggesting that other genes within 16q22.1 are involve d in the development of this tumor subtype. The high-resolution map present ed in this study provides a valuable resource for identification of tumor s uppressor genes expected to be involved in the etiology of breast carcinoma s. (C) 2000 Academic Press.