TTC4, a novel human gene containing the tetratricopeptide repeat and mapping to the region of chromosome 1p31 that is frequently deleted in sporadic breast cancer

The 1p31 region shows loss of heterozygosity in up to 50% of human breast c ancers, 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 chrom osomes spanning the critical region of 1p31. One of these ESTs was localize d within the contig to the region most commonly undergoing loss of heterozy gosity in breast cancer. The corresponding gene sequence for this EST was e stablished by cDNA cloning and RACE procedures. This gene is 2 kb long and contains a tetratricopeptide repeat moth and a coiled-coil domain. This fam ily 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 w e have named this gene TTC4. Northern blot analysis demonstrates a ubiquito us pattern of gene expression that includes breast tissue. A preliminary sc reen 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 mo re extensive analysis is warranted to establish whether subtle mutations ar e present in breast cancers. (C) 1999 Academic Press.