Genomic structure of the human tetratricopeptide repeat-containing gene, TTC4, from chromosome region 1p31 and mutation analysis in breast cancers

Loss of heterozygosity (LOH) in 1p31 is a frequent genetic alteration in br east tumors indicating the site of a tumor suppressor gene. We recently iso lated a new member of the human tetratricopeptide repeat-containing family of genes, TTC4, which maps to this region. Other members of this gene famil y have been implicated in tumorigenesis suggesting that TTC4 may represent a breast cancer tumor suppressor gene. We now report the exon/intron struct ure of TTC4 and single strand conformation polymorphism (SSCP) analysis of DNA from 20 sporadic breast tumors. Although polymorphic variations were id entified no mutations affecting the open reading frame of TTC4 were detecte d. Since the overall region of chromosome 1p31 which undergoes LOH can be r elatively large, excluding involvement of newly isolated genes from this re gion in breast cancer tumorigenesis is an important process for the success ful identification of the critical gene. Understanding the structure of TTC 4 now makes mutation analysis possible for other cancers and diseases that map to this region.