FHIT proteins and nucleic acids and methods based thereon

Abstract

The present invention relates to nucleotide sequences of FHIT genes and amino acid sequences of their encoded proteins, as well as derivatives and analogs thereof, and antibodies thereto. The FHIT gene sequence is mutated in diseases involving cell overproliferation, particularly malignancies of the digestive tract. The present invention further relates to the use of FHIT genes and their encoded proteins as diagnostic and therapeutic reagents for the detection and treatment of disease states associated with cell overproliferation.

What is claimed is:  
     
         1 . An antibody which specifically binds to a Fhit protein or derivative thereof.  
     
     
         2 . The antibody of  claim 1 , which is a monoclonal antibody.  
     
     
         3 . The antibody of  claim 1 , which is a polyclonal antibody.  
     
     
         4 . The antibody of  claim 1 , which is a chimeric antibody.  
     
     
         5 . The antibody of  claim 1 , which is a human antibody.  
     
     
         6 . The antibody of  claim 1 , which is a single chain antibody.  
     
     
         7 . The antibody of  claim 1 , which is a fragment.  
     
     
         8 . The antibody of  claim 7 , which is an Fab fragment.  
     
     
         9 . The antibody of  claim 7 , which is an Fab′ fragment.  
     
     
         10 . The antibody of  claim 7 , which is an F(ab′) 2  fragment.  
     
     
         11 . The antibody of  claim 1 , which is labeled with a detectable marker.  
     
     
         12 . The antibody of  claim 11 , wherein the detectable marker is selected from the group consisting of an enzyme, a radiolabel, a fluorescent molecule, a chemiluminescent molecule, a cofactor, an enzyme substrate, an enzyme inhibitor, and a magnetic particle.  
     
     
         13 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and the antibody of  claim 1 .  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the carrier or excipient comprises saline, dextrose, water, glycerol, ethanol, or combinations thereof.  
     
     
         15 . The pharmaceutical composition of  claim 13 , wherein the carrier or excipient comprises a sterile isotonic aqueous buffer.  
     
     
         16 . A kit comprising the antibody of  claim 1 .  
     
     
         17 . The kit of  claim 16 , further comprising a labeled binding partner to the antibody.  
     
     
         18 . The kit comprising the antibody of  claim 11 .  
     
     
         19 . An antibody which specifically binds to a mutant Fhit protein.  
     
     
         20 . The antibody of  claim 19 , wherein the antibody specifically binds to an epitope that is present in a Fhit deletion mutant, wherein said epitope is formed by the fusion of non-contiguous sequences that are not present in a wild-type Fhit protein.  
     
     
         21 . The antibody of  claim 20 , wherein the antibody neutralizes an activity of the mutant Fhit protein but does not neutralize the activity of a wild-type Fhit protein.