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. 1996 Feb 23;84(4):587-97. doi: 10.1016/s0092-8674(00)81034-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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 / genetics
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Esophageal Neoplasms / genetics
  • Exons / genetics
  • Gastrointestinal Neoplasms / genetics*
  • Gene Deletion
  • Genes, Neoplasm*
  • Humans
  • Hydrolases*
  • Kidney Neoplasms / genetics*
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Polymerase Chain Reaction
  • Proteins / genetics*
  • RNA, Messenger / genetics
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Stomach Neoplasms / genetics
  • Translocation, Genetic*
  • Tumor Cells, Cultured / physiology

Substances

  • DNA, Complementary
  • Neoplasm Proteins
  • Proteins
  • RNA, Messenger
  • fragile histidine triad protein
  • histidine triad protein
  • Hydrolases
  • Acid Anhydride Hydrolases

Associated data

  • GENBANK/U46922
  • GENBANK/U76262
  • GENBANK/U76263
  • GENBANK/U76264
  • GENBANK/U76265
  • GENBANK/U76266
  • GENBANK/U76267
  • GENBANK/U76268
  • GENBANK/U76269
  • GENBANK/U76270
  • GENBANK/U76271
  • GENBANK/U76272
  • GENBANK/U76273
  • GENBANK/U76274
  • GENBANK/U76275
  • GENBANK/U76276
  • GENBANK/U76277
  • GENBANK/U76278
  • GENBANK/U76279
  • GENBANK/U76280
  • GENBANK/U76281
  • GENBANK/U76282
  • GENBANK/U76283
  • GENBANK/U76284
  • GENBANK/U76285
  • GENBANK/U76286
  • GENBANK/U76287
  • GENBANK/U76288
  • GENBANK/U76289
  • GENBANK/U76290