Loss of heterozygosity events impeding breast cancer metastasis contain the MTA1 gene

Breast cancer mortality is seldom attributable to the primary tumor, but ra ther to the presence of systemic (metastatic) disease. Axillary lymph node dissection can identify the presence of metastatic breast cancer cells and serves as a marker for systemic disease. Previous work in our laboratory de termined that rates of loss of heterozygosity (LOH) of a 1.6-Mb region of c hromosome 14q 31.2 is much higher in axillary lymph node-negative primary b reast tumors than in axillary lymph node-positive primary breast tumors (P. O'Connell et al., J, Natl, Cancer Inst,, 91: 1391-1397, 1999,, This unusua l observation suggests that, whereas the LOH of this region promotes primar y breast cancer formation, some gene(s) mapping to this 1.6-Mb region is ra te-limiting for breast cancer metastasis. Thus, if primary breast cancers d elete this region, their ability to metastasize decreases, To identify this gene(s), we have physically mapped this area of chromosome 14q, confirmed the position of two known genes and 13 other expressed sequence tags into t his 1.6-Mb region. One of these, the metastasis-associated 1 (MTA1) gene, p reviously identified as a metastasis-promoting gene (Y. Toh rt al., J, Biol , Chem,, 269: 22958-22963, 1994.), mapped to the center of our 1.6-Mb targe t region. Thus, MTA1 represents a strong candidate for this breast cancer m etastasis-promoting gene.