title: The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers.
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.
authors.affiliation: Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: M G
authors.initials: MG
authors.lastname: Cotticelli
authors.forename: K
authors.initials: K
authors.lastname: Kastury
authors.forename: R
authors.initials: R
authors.lastname: Baffa
authors.forename: J
authors.initials: J
authors.lastname: Palazzo
authors.forename: Z
authors.initials: Z
authors.lastname: Siprashvili
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: P
authors.initials: P
authors.lastname: McCue
authors.forename: T
authors.initials: T
authors.lastname: Druck
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: K
authors.initials: K
authors.lastname: Huebner
mesh_terms: D017766:Acid Anhydride Hydrolases; D000595:Amino Acid Sequence; D001483:Base Sequence; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002898:Chromosomes, Human, Pair 8; D003110:Colonic Neoplasms / Q000235:genetics; D003360:Cosmids / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004938:Esophageal Neoplasms / Q000235:genetics; D005091:Exons / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D017353:Gene Deletion; D052138:Genes, Neoplasm; D006801:Humans; D006867:Hydrolases; D007680:Kidney Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013274:Stomach Neoplasms / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000502:physiology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D018076:DNA, Complementary; D006867:Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase; C097552:histidine triad protein