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PMID: 8598045 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 ·Vol. 84 ·No. 4 ·1996-02-23 ·Pages 587-97

Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, Croce CM, Huebner K

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.

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,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

Chemicals

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

Authors & Affiliations

12 authors, click to expand affiliations / ORCID

Ohta M

Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA.

Inoue H

Cotticelli M G

Kastury K

Baffa R

Palazzo J

Siprashvili Z

Mori M

McCue P

Druck T

Croce C M

Huebner K

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)81034-x

Published

1996-02-23

Pages

587-97

Language

English

Region

United States

NLM ID

0413066

Subset

Grants

NCI NIH HHS · CA21124 · United States

NCI NIH HHS · CA39860 · United States

NCI NIH HHS · CA51083 · United States

Databases

GENBANK

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

External Links

PubMed source DOI: 10.1016/s0092-8674(00)81034-x View journal details

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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.

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