Compositions and methods for the diagnosis, prevention and treatment of tumor progression

Abstract

The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of tumor progression in cells involved in human tumors such as melanomas, breast, gastrointestinal, lung, and bone tumors, various types of skin cancers, and other neoplastic conditions such as leukemias and lymphomas. Genes are identified that are differentially expressed in benign (e.g., non-malignant) tumor cells relative to malignant tumor cells exhibiting a high metastatic potential. Genes are also identified via the ability of their gene products to interact with gene products involved in the progression to, and/or aggressiveness of, neoplastic tumor disease states. The genes and gene products identified can be used diagnostically or for therapeutic intervention.

What is claimed is:  
     
         1 . An isolated nucleic acid comprising the nucleotide sequence SEQ ID NO:2 as depicted in FIG. 3, or the nucleotide sequence of a gene or gene fragment contained in the following clone as deposited with the NRRL: pFOMY030 (NRRL accession No. B-21416).  
     
     
         2 . An isolated nucleic acid which encodes the amino acid sequence depicted in FIG. 3 from amino acid residue number 1 to 542, or its complement.  
     
     
         3 . An isolated nucleic acid which hybridizes to an isolated nucleic acid which encodes the amino acid sequence depicted in FIG. 3 from amino acid residue number 1 to 542, or its complement.  
     
     
         4 . A genetically engineered host cell comprising the nucleotide sequence of  claim 2 .  
     
     
         5 . An expression vector comprising the nucleotide sequence of  claim 2  in operative association with a nucleotide sequence regulatory element that controls expression of the nucleotide sequence in a host cell.  
     
     
         6 . A substantially pure gene product encoded by the nucleic acid of  claim 3 .  
     
     
         7 . An isolated nucleic acid comprising the nucleotide sequence SEQ ID NO:6 as depicted in FIG. 5, or SEQ ID NO:8 as depicted in FIG. 6.  
     
     
         8 . An isolated nucleic acid which encodes the amino acid sequence depicted in FIG. 5 from amino acid residue number 1 to 1497, or its complement.  
     
     
         9 . An isolated nucleic acid which encodes the amino acid sequence depicted in FIG. 6 from amino acid residue number 1 to 1533, or its complement.  
     
     
         10 . An isolated nucleic acid which hybridizes to a nucleic acid that encodes the amino acid sequence depicted in FIG. 5 from amino acid residue number 1 to 1497 (SEQ ID NO:7), or its complement, or the amino acid sequence depicted in FIG. 6 from amino acid residue number 1 to 1533 (SEQ ID NO:9), or its complement.  
     
     
         11 . A nucleotide vector containing the nucleotide sequence of  claim 10 .  
     
     
         12 . A genetically engineered host cell containing the nucleotide sequence of  claim 10 .  
     
     
         13 . An expression vector containing the nucleotide sequence of  claim 10  in operative association with a nucleotide sequence regulatory element that controls expression of the nucleotide sequence in a host cell.  
     
     
         14 . A substantially pure gene product encoded by the nucleic acid of  claim 10 .  
     
     
         15 . An antibody that immunospecifically binds the gene product of  claim 14 .  
     
     
         16 . A method of diagnosing tumor progression in a mammal, said method comprising: 
 obtaining a test sample of tissue cells from the mammal;    obtaining a control sample of known normal cells from the same type of tissue; and    detecting in both the test sample and the control sample the level of expression of a gene transcript or gene product of gene 030, wherein a level of expression lower in the test sample than in the control sample indicates a tumor progression state in the test sample.    
     
     
         17 . A method for treating tumor progression in a mammal, said method comprising administering to the mammal a compound in an amount effective to increase the level of expression or activity of a gene transcript or gene product of gene 030 in cells exhibiting a tumor progression state, to a level effective to ameliorate symptoms of the tumor progression state.  
     
     
         18 . A method of  claim 17 , wherein the compound comprises a nucleic acid whose administration results in an increase in the level of the differentially expressed gene transcript and gene product in the cells in the tumor progression state, thereby ameliorating symptoms of the tumor progression state.  
     
     
         19 . A method of  claim 18 , wherein the nucleic acid comprises a nucleic acid of gene 030.  
     
     
         20 . A method of  claim 17 , wherein the compound is a 030 gene product.  
     
     
         21 . A method of  claim 17 , wherein the tumor progression state is neoplasia.  
     
     
         22 . A method of  claim 17 , wherein the tumor progression state is metastasis.  
     
     
         23 . A method for inhibiting tumor progression in a mammal, said method comprising administering to the mammal a normal allele of a 030 gene so that the normal gene product is expressed, thereby inhibiting tumor progression.  
     
     
         24 . A method of  claim 23 , wherein the tumor progression is metastasis.  
     
     
         25 . A method for treating tumor progression in a mammal, said method comprising administering to the mammal an effective amount of a 030 gene product.  
     
     
         26 . A method of  claim 25 , wherein the tumor progression is metastasis.  
     
     
         27 . A method of monitoring the efficacy of a compound in clinical trials for inhibition of tumor progression in a patient, said method comprising obtaining a first sample of tumor tissue cells from the patient; 
 administering the compound to the patient;    after a time sufficient for the compound to inhibit tumor progression, obtaining a second sample of tumor tissue cells from the patient; and    detecting in the first and second samples the level of expression of a 030 gene transcript or product, wherein a level of expression higher in the second sample than in the first sample indicates that the compound is effective to inhibit tumor progression in the patient.    
     
     
         28 . A method of  claim 27 , wherein the 030 gene transcript or gene product is differentially expressed in individuals predisposed to a metastatic neoplastic disease.