Novel tumor marker

Abstract

The present invention concerns a gene product largely homologous to the epithelial growth factor receptor (EGFR). It further refers to mRNA coding for such epithelial growth factor receptor. The present invention provides such an epithelial growth factor receptor which is characterized in that either exons 12 to 14 or exons 12 to 15 are deleted. These novel variants of the epithelial growth factor receptor can be used for a diagnosis, stratification, therapy guidance of a tumor or therapy guidance of tumor surgery.

1 . A gene product largely homologous to the epithelial growth factor receptor (EGFR), characterized in that the amino acids encoded by either exons 12 to 14 or exons 12 to 15 are deleted. 
     
     
         2 . The gene product according to  claim 1 , characterized in that it comprises the following amino acid sequence: 
       
         
           
                 
                 
               
                   (SEQ ID NO:5) 
                     
                 
                 
                 
               
                   NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAW 
                     
                 
                     
                 
                   PENRTDLHAFENLEIIRGRTKQQDQTTVSSVPTTLTAPTASRPARQESWE 
                 
                     
                 
                   KTTPWSGSTQTPAMCATCAIQTAPTDALGQVLKAVQR. 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
         3 . The gene product according to  claim 2 , characterized in that it comprises the following amino acid sequence: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO:4)  
                 
                 
                 
               
                   NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAW 
                     
                 
                     
                 
                   PENRTDLHAFENLEIIRGRTKQQDQTTVSSVPTTLTAPTASRPARQESWE 
                 
                     
                 
                   KTTPWSGSTQTPAMCATCAIQTAPTDALGQVLKAVQRMGLRSRPSPLGWW 
                 
                     
                 
                   GPSSCCWWWPWGSASSCEGATSFGSARCGGCCRRGSLWSLLHPVEKLPT 
                 
                     
                 
                   KLS. 
                 
             
                
               
            
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . The gene product according to  claim 1 , characterized in that it comprises the following amino acid sequence: 
       
         
           
                 
                 
               
                   (SEQ ID NO:3) 
                     
                 
                 
                 
               
                   NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAW 
                     
                 
                     
                 
                   PENRTDLHAFENLEIIRGRTKQQCTGPGLEGCPTN. 
                 
             
                
               
            
             
                
                
                
               
            
           
         
       
     
     
         5 . The gene product according to  claim 1 , characterized in that with the exception of said deleted exons, its amino acid sequence is largely homologous or identical to the epithelial growth factor receptor in its native state (wild-type) or any of its known variants or derivatives. 
     
     
         6 . The gene product according to  claim 1 , characterized in that with the exception of said deleted exons, its amino acid sequence is largely homologous or identical to variants vI, vII, vIII, vIII/Δ12-13, TDM/2-7, vIV, vV, TDM/18-25, TDM/18-26. 
     
     
         7 . The gene product according to  claim 1 , characterized in that it comprises further amino acid sequence modifications, like such as caused by single nucleotide mutations or nucleotide deletions in its corresponding gene or mRNA etc. 
     
     
         8 . A gene coding for a gene product according to  claim 1 . 
     
     
         9 . A polynucleotide largely homologous or identical to the messenger ribonucleic acid (mRNA) coding for the epithelial growth factor receptor (EGFR), wherein the nucleotides coding for exons 12 to 14 or exons 12 to 15 of the epithelial growth factor receptor (EGFR) are deleted. 
     
     
         10 . The polynucleotide according to  claim 9 , characterized in that it comprises a nucleotide sequence corresponding to the following cDNA-Sequence (SEQ ID NO:1): 
       
         
           
                 
                 
               
                   AAACTGCACCTCCATCAGTGGCGATCTCCACATCCTGCCGGTGGCATTTA 
                     
                 
                     
                 
                   GGGGTGACTCCTTCACACATACTCCTCCTCTGGATCCACAGGAACTGGAT 
                 
                     
                 
                   ATTCTGAAAACCGTAAAGGAAATCACAGGGTTTTTGCTGATTCAGGCTTG 
                 
                     
                 
                   GCCTGAAAACAGGACGGACCTCCATGCCTTTGAGAACCTAGAAATCATAC 
                 
                     
                 
                   GCGGCAGGACCAAGCAACAGGACCAGACAACTGTATCCAGTGTGCCCACT 
                 
                     
                 
                   ACATTGACGGCCCCCACTGCGTCAAGACCAGCCCGGCAGGAGTCATGGGA 
                 
                     
                 
                   GAAAACAACACCCTGGTCTGGAAGTACGCAGACGCCGGCCATGTGTGCCA 
                 
                     
                 
                   CCTGTGCCATCCAAACTGCACCTACGGATGCACTGGGCCAGGTCTTGAAG 
                 
                     
                 
                   GCTGTCCAACGAAT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         11 . The polynucleotide according to  claim 9 , characterized in that it comprises a nucleotide sequence corresponding to the following cDNA-Sequence (SEQ ID NO:2): 
       
         
           
                 
                 
               
                   AAACTGCACCTCCATCAGTGGCGATCTCCACATCCTGCCGGTGGCATTTA 
                     
                 
                     
                 
                   GGGGTGACTCCTTCACACATACTCCTCCTCTGGATCCACAGGAACTGGAT 
                 
                     
                 
                   ATTCTGAAAACCGTAAAGGAAATCACAGGGTTTTTGCTGATTCAGGCTTG 
                 
                     
                 
                   GCCTGAAAACAGGACGGACCTCCATGCCTTTGAGAACCTAGAAATCATAC 
                 
                     
                 
                   GCGGCAGGACCAAGCAACAATGCACTGGGCCAGGTCTTGAAGGCTGTCCA 
                 
                     
                 
                   ACGAAT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The polynucleotide according to  claim 9 , characterized in that with the exception of the nucleotides coding for said deleted exons its nucleotide sequence is largely homologous or identical to the mRNA coding for the epithelial growth factor receptor in its native state (wild-type) or any of its known variants or derivatives. 
     
     
         13 . The polynucleotide according to the  claim 12 , characterized in that with the exception of the nucleotides coding for said deleted exons its nucleotide sequence is largely homologous or identical to variants vI, vII, vIII, vIII/Δ12-13, TDM/2-7, vIV, vV, TDM/18-25, TDM/18-26. 
     
     
         14 . The polynucleotide according to  claim 9 , characterized in that it comprises further nucleotide sequence modifications, like single nucleotide modifications, nucleotide deletions etc. 
     
     
         15 . A method for detecting the presence of a tumor, comprising (a) analyzing a sample for the presence of a gene product, a gene and/or a polynucleotide that comprises or codes for gene product largely homologous to epithelial growth factor receptor (EGFR) that lacks either exons 12 to 14 or exons 12 to 15 or the corresponding amino acid sequences, and (b) deciding on the presence of a tumor if presence of a gene product or polynucleotide is detected. 
     
     
         16 . The method according to  claim 15 , further comprising diagnosing, stratifying or guiding therapy of a tumor or after tumor surgery. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The method according to claim  17 , characterized in that the tumor is an epithelial tumor, e.g. colon cancer, lung cancer, prostate cancer, breast cancer or other solid tumors. 
     
     
         20 . A method for targeting a tumor cell with a therapeutic agent comprising (a) providing a composition a gene product, a gene and/or a polynucleotide that comprises or codes for gene product largely homologous to epithelial growth factor receptor (EGFR) that lacks either exons 12 to 14 or exons 12 to 15 or the corresponding amino acid sequences, wherein said gene product, gene or polynucleotide is linked to or further codes for said therapeutic agent, and (b) delivering said composition to said tumor cell.