The 1p31 region shows loss of heterozygosity in up to 50% of human breast cancers, indicating the presence of a tumor suppressor gene in this location. We have mapped six novel ESTs to a 15-Mb contig of yeast artificial chromosomes spanning the critical region of 1p31. One of these ESTs was localized within the contig to the region most commonly undergoing loss of heterozygosity in breast cancer. The corresponding gene sequence for this EST was established by cDNA cloning and RACE procedures. This gene is 2 kb long and contains a tetratricopeptide repeat motif and a coiled-coil domain. This family of genes has been implicated in a wide variety of functions, including tumorigenesis. This is the fourth member of the human gene family, and so we have named this gene TTC4. Northern blot analysis demonstrates a ubiquitous pattern of gene expression that includes breast tissue. A preliminary screen of human breast cancer cell lines shows that TTC4 is expressed in all cases, but SSCP analysis of the coding region of this gene following RT-PCR failed to reveal any mutations. Clearly, because of its map location, a more extensive analysis is warranted to establish whether subtle mutations are present in breast cancers.
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