Methods for the diagnosis and treatment of lung cancer

Abstract

The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell, and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.

1 . A method for detecting and diagnosing of the neoplastic condition of a lung cell, comprising detecting the presence of an overexpressed proto-oncogene selected from the group consisting of b-myb, p67, PGP9.5 and 8-oxo-dGTPase, in a lung cell sample, wherein the overexpression is indicative of the neoplastic condition of the lung cell.  
     
     
         2 . The method of  claim 1 , wherein the proto-oncogene is b-myb.  
     
     
         3 . The method of  claim 1 , wherein the proto-oncogene is PGP9.5.  
     
     
         4 . The method of  claim 1 , wherein the proto-oncogene is 8-oxo-dGTPase.  
     
     
         5 . The method of  claim 1 , wherein the proto-oncogene is p67.  
     
     
         6 . The method of  claim 1 , wherein the presence of the overexpressed proto-oncogene is determined by detecting the quantity of mRNA transcribed from the proto-oncogene.  
     
     
         7 . The method of  claim 2 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence TGCTGCCCTG (SEQ. ID No. 1) or its complement.  
     
     
         8 . The method of  claim 3 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence is CAGTCTAAAA (SEQ. ID No. 2) or its complement.  
     
     
         9 . The method of  claim 4 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence TGGCCCGACG (SEQ. ID No. 3) or its complement.  
     
     
         10 . The method of  claim 5 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence TAATACTTTT (SEQ ID NO. 4) or its complement.  
     
     
         11 . The method of  claim 6 , wherein the presence of the overexpressed proto-oncogene is determined by detecting the quantity of cDNA produced from the reverse transcription of the mRNA.  
     
     
         12 . The method of  claim 1 , wherein the presenece of the overexpressed proto-oncogene is determined by detecting the quantity of the polypeptide or protein encoded by the proto-oncogene.  
     
     
         13 . The method of  claim 12 , wherein the lung cancer is non-small cell lung cancer.  
     
     
         14 . A screen for a potential therapeutic agent for the reversal of the neoplastic condition of a lung cell wherein the cell is characterized by overexpression of a proto-oncogene selected from the group consisting of b-myb, p67, PGP9.5 and 8-oxo-dGTPase comprising contacting a sample with an effective amount of a potential agent and assaying for reversal of the neoplastic condition.  
     
     
         15 . The screen of  claim 14 , wherein the proto-oncogene is b-myb.  
     
     
         16 . The method of  claim 14 , wherein the proto-oncogene is PGP9.5.  
     
     
         17 . The method of  claim 14 , wherein the proto-oncogene is 8-oxo-dGTPase.  
     
     
         18 . The method of  claim 14 , wherein the proto-oncogene is p67.  
     
     
         19 . A method for reversing the neoplastic condition of a lung cell, wherein the cell is characterized by overexpression of a proto-oncogene comprising contacting the cell with an agent identified by the method of  claim 14 .  
     
     
         20 . The method of  claim 19 , wherein the proto-oncogene is b-myb.  
     
     
         21 . The method of  claim 19 , wherein the proto-oncogene is PGP9.5.  
     
     
         22 . The method of  claim 19 , wherein the proto-oncogene is 8-oxo-dGTPase.  
     
     
         23 . The method of  claim 19 , wherein the proto-oncogene is p67.  
     
     
         24 . The method of claims  19 , wherein the agent is anti-sense RNA that specifically inhibits the overexpression of the proto-oncogene.  
     
     
         25 . A probe or primer to detect the presence of b-myb, comprising sequence TGCTGCCCTG (SEQ. ID No. 1) or its complement.  
     
     
         26 . A probe or primer to detect the presence of PGP9.5, comprising sequence CAGTCTAAAA (SEQ. ID No. 2) or its complement.  
     
     
         27 . A probe or primer to detect the presence of 8-oxo-dGTPase, comprising sequence TGGCCCGACG (SEQ. ID No. 3) or its complement.  
     
     
         28 . A probe or primer to detect the presence of p67, comprising sequence TAATACTTTT (SEQ ID NO. 4) or its complement.  
     
     
         29 . A solid phase support comprising the probes or primers of claims through  28 , or their complements.  
     
     
         30 . A kit for use in a diagnostic method according to  claim 1  comprising in suitable packaging: 
 one or more polynucleotides selected from the group consisting of b-myb, p67, PGP9.5 and 8-oxo-dGTPase immobilized on a solid support and    a reagent suitable for hybridizing a sample suspected of containing the lung cancer cell.    
     
     
         31 . A method for identifying a patient predisposed to developing lung cancer, comprising detecting the expression level of the b-myb proto-oncogene in a sample isolated from the patient, wherein the presence of overexpression of the b-myb proto-oncogene identifies the patient as predisposed to developing lung cancer.  
     
     
         32 . The method of  claim 31 , further comprising detecting the expression level of a proto-oncogene of the group consisting of p77, PGP9.5 and 8-oxo-dGTPase, wherein the overexpression of at least one of the proto-oncogenes identifies the patient as predisposed to developing lung cancer.