Two distinct tumor suppressor loci within chromosome 11p15 implicated in breast cancer progression and metastasis
Abstract
Chromosome 11p15 has attracted considerable attention because of the biological importance of this region to human disease. Apart from being an important tumor suppressor locus showing loss of heterozygosity (LOH) in several adult and childhood cancers, 11p15 has been shown by linkage analysis to harbor the gene(s) for the Beckwith-Wiedemann syndrome. Furthermore, the clustering of known imprinted genes in the 11p15.5 region suggests that the target gene may also be imprinted. However, positional cloning efforts to identify the target genes have been complicated by the large size (approximately 10 Mb) and complexity of LOH at 11p15. Here, we have analyzed 94 matched normal and breast tumor samples using 17 polymorphic markers that map to 11p15.5-15.4. We have defined precisely the location of a breast tumor suppressor gene between the markers D11S1318 and D11S4088 (approximately 500 kb) within 11p15.5. LOH at this region occurred in approximately 35-45% of breast tumors analyzed. In addition, we have fine-mapped a second, critical region of LOH, that spans the markers D11S1338-D11S1323 (approximately 336 kb) at 11p15.5-p15.4, that is lost in approximately 55-60% of breast tumors. There is a striking correlation between the loss...Continue Reading
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