Oncokinase fusion polypeptides associated with hyperproliferative and related disorders, nucleic acids encoding the same and methods for detecting and identifying the same

Abstract

Oncokinase fusion polypeptides associated with hyperproliferative disorders and the polynucleotides encoding for such fusion polypeptides are provided. The fusion polypeptides have a C-terminal tyrosine kinase domain fused to an N-terminal domain that is not normally fused to the C-terminal tyrosine kinase domain and they possess constitutively activated tyrosine kinase activity. Also provided are methods for detecting and identifying the fusion polypeptides and polynucleotides and methods of diagnosing disease conditions associated with the fusion polypeptides and polynucleotides. In addition, screening assays for identifying agents useful for treating disease conditions associated with such fusion polypeptides and polynucleotides are provided. Furthermore, methods of treating disease conditions associated with the presence of the fusion polypeptides are provided.

1 . A fusion polypeptide comprising a C-terminal tyrosine kinase domain and an N-terminal domain wherein said fusion polypeptide has a constitutively activated kinase activity, is present in other than its naturally occurring environment and is further characterized by at least one of the following features:
 (a) said C-terminal domain is from a chromosome 4 encoded protein;   (b) said N-terminal domain is from a chromosome 4 encoded protein; and   (c) said fusion protein is not a product of a translocation event.   
     
     
         2 . The fusion polypeptide according to  claim 1 , wherein said C-terminal domain is from a chromosome 4 encoded protein. 
     
     
         3 . The fusion polypeptide according to  claim 1 , wherein said N-terminal domain is from a chromosome 4 encoded protein. 
     
     
         4 . The fusion polypeptide according to  claim 1 , wherein said fusion protein is not a product of a translocation event. 
     
     
         5 . The fusion polypeptide according to  claim 1 , wherein said chromosome 4 tyrosine kinase domain comprises the C-terminal domain of a tyrosine kinase chosen from PDGFRα, c-Kit and VEGFR-2. 
     
     
         6 . The fusion polypeptide according to  claim 1 , wherein said tyrosine kinase is PDGFRα. 
     
     
         7 . The fusion polypeptide according to  claim 1 , wherein said N-terminal domain is a NM — 030917 domain. 
     
     
         8 . The fusion polypeptide according to  claim 1 , wherein said fusion polypeptide is a primate polypeptide. 
     
     
         9 . The fusion polypeptide according to  claim 8 , wherein said primate polypeptide is a human polypeptide. 
     
     
         10 . The fusion polypeptide according to  claim 1 , wherein said fusion polypeptide has an amino acid sequence that is substantially the same as or identical to a sequence chosen from SEQ ID NO:01, SEQ ID NO:02; SEQ ID NO:03 and SEQ ID NO:04. 
     
     
         11 . The fusion polypeptide according to  claim 1 , wherein said fusion polypeptide is substantially pure. 
     
     
         12 - 53 . (canceled)