Reciprocal translocations in breast tumor cell lines: cloning of a t(3;20) that targets the FHIT gene.
All molecular alterations that lead to breast cancer are not precisely known. We are evaluating the frequency and consequences of reciprocal translocations in breast cancer. We surveyed 15 mammary cell lines by multicolor fluorescence in situ hybridization (M-FISH). We identified nine apparently reciprocal translocations. Using mBanding FISH and FISH with selected YAC clones, we identified the breakpoints for four of them, and cloned the t(3;20)(p14;p11) found in the BrCa-MZ-02 cell line. We found that the breakpoint targets the potential tumor-suppressor gene FHIT (fragile histidine triad) in the FRA3B region; it is accompanied by homozygous deletion of exon 5 of the gene and absence of functional FHIT and fusion transcripts, which leads to the loss of FHIT protein expression. Additional experiments using comparative genomic hybridization provided further information on the genomic context in which the t(3;20)(p14;p11) reciprocal translocation was found.
D017766:Acid Anhydride Hydrolases; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002871:Chromosome Banding; D019457:Chromosome Breakage / Q000235:genetics; D002872:Chromosome Deletion; D002873:Chromosome Fragility / Q000235:genetics; D002874:Chromosome Mapping; D020223:Chromosome Painting; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003001:Cloning, Molecular / Q000379:methods; D005091:Exons / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D005819:Genetic Markers; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase