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      The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers.

      Cell
      Acid Anhydride Hydrolases, Amino Acid Sequence, Base Sequence, Chromosome Fragile Sites, Chromosome Fragility, Chromosome Mapping, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 8, Colonic Neoplasms, genetics, Cosmids, DNA, Complementary, isolation & purification, Esophageal Neoplasms, Exons, Gastrointestinal Neoplasms, Gene Deletion, Genes, Neoplasm, Humans, Hydrolases, Kidney Neoplasms, Molecular Sequence Data, Neoplasm Proteins, Polymerase Chain Reaction, Proteins, RNA, Messenger, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Stomach Neoplasms, Translocation, Genetic, Tumor Cells, Cultured, physiology

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          Abstract

          A 200-300 kb region of chromosome 3p14.2, including the fragile site locus FRA3B, is homozygously deleted in multiple tumor-derived cell lines. Exon amplification from cosmids covering this deleted region allowed identification of the human FHIT gene, a member of ther histidine triad gene family, which encodes a protein with 69% similarity to an S. pombe enzyme, diadenosine 5', 5''' P1, P4-tetraphosphate asymmetrical hydrolase. The FHIT locus is composed of ten exons distributed over at least 500 kb, with three 5' untranslated exons centromeric to the renal carcinoma-associated 3p14.2 breakpoint, the remaining exons telomeric to this translocation breakpoint, and exon 5 within the homozygously deleted fragile region. Aberrant transcripts of the FHIT locus were found in approximately 50% of esophageal, stomach, and colon carcinomas.

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