Novel human genes and gene expression products

Abstract

This invention relates to novel human genes, to proteins expressed by the genes, and to variants of the proteins. The invention also relates to diagnostic assays and therapeutic agents related to the genes and proteins, including probes, antisense constructs, and antibodies. The subject nucleic acids have been found to be differentially regulated in tumor cells, particularly colon cancer cell lines and/or tissue.

We claim:  
     
         1 . An isolated nucleic acid comprising a nucleotide sequence which hybridizes under stringent conditions to a sequence of SEQ ID Nos. 1-127 or a sequence complementary thereto.  
     
     
         2 . An isolated nucleic acid comprising a nucleotide sequence at least 80% identical to a sequence corresponding to at least about 15 consecutive nucleotides of one of SEQ ID Nos. 1-127 or a sequence complementary thereto.  
     
     
         3 . An isolated nucleic acid comprising a nucleotide sequence of SEQ ID Nos. 1-127 or a sequence complementary thereto.  
     
     
         4 . A nucleic acid according to  claim 1 , further comprising a transcriptional regulatory sequence operably linked to said nucleotide sequence so as to render said nucleotide sequence suitable for use as an expression vector.  
     
     
         5 . An expression vector, capable of replicating in at least one of a prokaryotic cell and eukaryotic cell, comprising the nucleic acid of  claim 4 .  
     
     
         6 . A host cell transfected with the expression vector of  claim 5 .  
     
     
         7 . A transgenic animal having a transgene of the nucleic acid of  claim 1  incorporated in cells thereof, which transgene modifies the level of expression of the nucleic acid, the stability of an mRNA transcript of the nucleic acid, or the activity of the encoded product of the nucleic acid.  
     
     
         8 . A substantially pure nucleic acid which hybridizes under stringent conditions to a nucleic acid probe corresponding to at least 12 consecutive nucleotides of one of SEQ ID Nos. 1-127 or a sequence complementary thereto.  
     
     
         9 . A polypeptide including an amino acid sequence encoded by a nucleic acid of  claim 1  or a fragment comprising at least 25 amino acids thereof.  
     
     
         10 . A probe/primer comprising a substantially purified oligonucleotide, said oligonucleotide containing a region of nucleotide sequence which hybridizes under stringent conditions to at least 12 consecutive nucleotides of sense or antisense sequence selected from SEQ ID Nos. 1-127.  
     
     
         11 . An array including at least 10 different probes of  claim 10  attached to a solid support.  
     
     
         12 . The probe/primer of  claim 10 , further comprising a label group attached thereto and able to be detected.  
     
     
         13 . The probe/primer of  claim 12 , wherein said label group being selected from radioisotopes, fluorescent compounds, enzymes, and enzyme co-factors.  
     
     
         14 . An antibody immunoreactive with a polypeptide of  claim 9 .  
     
     
         15 . An antisense oligonucleotide analog which hybridizes under stringent conditions to at least 12 consecutive nucleotides of one of SEQ ID Nos. 1-850 or a sequence complementary thereto, and which is resistant to cleavage by a nuclease.  
     
     
         16 . A test kit for determining the phenotype of transformed cells, comprising the probe/primer of  claim 12 , for measuring a level of a nucleic acid which hybridizes under stringent conditions to a nucleic acid of SEQ ID Nos. 1-850 in a sample of cells isolated from a patient.  
     
     
         17 . A test kit for determining the phenotype of transformed cells, comprising an antibody specific for a protein encoded by a nucleic acid which hybridizes under stringent conditions to any one of SEQ Nos. 1-850.  
     
     
         18 . A method of determining the phenotype of a cell, comprising detecting the differential expression, relative to a normal cell, of at least one nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-850, wherein the nucleic acid is differentially expressed by at least a factor of two.  
     
     
         19 . A method for determining the phenotype of cells in a sample of cells from a patient, comprising: 
 i. providing a nucleic acid probe comprising a nucleotide sequence having at least 12 consecutive nucleotides of any of SEQ ID Nos. 1-850;    ii. obtaining a sample of cells from a patient;    iii. providing a second sample of cells substantially all of which are non-cancerous;    iv. contacting the nucleic acid probe under stringent conditions with mRNA of each of said first and second cell samples; and    V. comparing (a) the amount of hybridization of the probe with mRNA of the first cell sample, with (b) the amount of hybridization of the probe with mRNA of the second cell sample, wherein a difference of at least a factor of two in the amount of hybridization with the mRNA of the first cell sample as compared to the amount of hybridization with the mRNA of the second cell sample is indicative of the phenotype of cells in the first cell sample.    
     
     
         20 . A method of determining the phenotype of a cell, comprising detecting the differential expression, relative to a normal cell, of at least one protein encoded by a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-850, wherein the protein is differentially expressed by at least a factor of two.  
     
     
         21 . The method of  claim 20 , wherein the level of said protein is detected in an immunoassay.  
     
     
         22 . A method for determining the presence or absence of a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-127 in a cell, comprising contacting the cell with a probe of  claim 10 .  
     
     
         23 . A method for determining the presence of absence of a polypeptide encoded by a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-127 in a cell, comprising contacting the cell with an antibody of  claim 14 .  
     
     
         24 . A method for detecting a mutation in a test nucleic acid which hybridizes under stringent conditions to a nucleic acid of SEQ ID Nos. 1-383 or a sequence complementary thereto, comprising 
 i. collecting a sample of cells from a patient,    ii. isolating nucleic acid from the cells of the sample,    iii. contacting the nucleic acid sample with one or more primers which specifically hybridize to a nucleic acid sequence of SEQ ID Nos. 1-383 under conditions such that hybridization and amplification of the nucleic acid occurs, and    iv. comparing the presence, absence, or size of an amplification product to the amplification product of a normal cell.    
     
     
         25 . A method for identifying an agent which alters the level of expression in a cell of a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-850 or a sequence complementary thereto, comprising 
 i. providing a cell;    ii. treating the cell with a test agent;    iii. determining the level of expression in the cell of a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-850 or a sequence complementary thereto; and    iv. comparing the level of expression of the nucleic acid in the treated cell with the level of expression of the nucleic acid in an untreated cell, wherein a change in the level of expression of the nucleic acid in the treated cell relative to the level of expression of the nucleic acid in the untreated cell is indicative of an agent which alters the level of expression of the nucleic acid in a cell.    
     
     
         26 . A pharmaceutical composition comprising an agent identified by the method of  claim 25 .  
     
     
         27 . A pharmaceutical composition comprising a nucleic acid which includes a nucleotide sequence which hybridizes under stringent conditions to one of SEQ ID Nos. 1-850 or a sequence complementary thereto.  
     
     
         28 . A pharmaceutical composition comprising a polypeptide encoded by a nucleic acid which includes a nucleotide sequence that hybridizes under stringent conditions to one of SEQ ID Nos. 1-850 or a sequence complementary thereto.  
     
     
         29 . An isolated nucleic acid comprising a portion of a nucleotide sequence of SEQ ID Nos. 128-383 or a sequence complementary thereto.  
     
     
         30 . A gene which hybridizes to one of SEQ ID Nos. 1-383.  
     
     
         31 . A method for detecting cancer in which one or more of SEQ ID Nos. 1-850 are used as probes, said method comprising: 
 i. collecting a sample of cells from a patient,    ii. isolating nucleic acid from the cells of the sample,    iii. contacting the nucleic acid sample with one or more primers which specifically hybridize to a nucleic acid sequence of SEQ ID Nos. 1-850 under conditions such that hybridization and amplification of the nucleic acid occurs, and    iv. comparing the presence, absence, or size of an amplification product to the amplification product of a normal cell.    
     
     
         32 . A method of  claim 31  in which said cancer is colon cancer.  
     
     
         33 . A method for detecting cancer in a patient sample in which an antibody to a protein encoded by SEQ ID Nos. 1-850 is used to react with proteins in said sample.  
     
     
         34 . A method of  claim 33  in which said cancer is colon cancer.