C-cbl mutations and uses thereof

Abstract

The present invention relates generally to the fields of molecular biology and growth factor regulation. The invention concerns methods and compositions useful for diagnosing and treating human lung cancer associated with mutated c-CBL.

1 . A method of identifying a subject that is susceptible to treatment with a c-Met inhibitor comprising determining whether a sample from the subject comprises a mutation in a nucleic acid sequence encoding human c-CBL, wherein the mutation results in an amino acid change at position S80N, H94Y, Q249E, V391I, 72515_72517delATG, W802*, R830K, A848T, L620F, P170L, S171S, L281F, L254S, or P782L. 
     
     
         2 . The method of  claim 1 , wherein the presence of a mutation in a nucleic acid sequence encoding human c-CBL identifies a subject that is susceptible to treatment with a c-Met inhibitor. 
     
     
         3 . The method of  claim 1 , wherein the absence of a mutation in a nucleic acid sequence encoding human c-CBL identifies a subject that is not susceptible to treatment with a c-Met inhibitor. 
     
     
         4 . The method of  claim 1 , wherein the subject has been diagnosed with cancer. 
     
     
         5 . The method of  claim 1 , wherein the subject has cancer. 
     
     
         6 . The method of  claim 1 , wherein the sample is a cancer sample. 
     
     
         7 . A method of identifying a subject that is susceptible to treatment with a c-Met inhibitor comprising determining whether a sample from the subject comprises a mutation in a nucleic acid sequence encoding human c-CBL, wherein the mutation is located in the TKB domain, RING finger domain, proline-rich region, C-terminal region, or other domain linkage regions of c-CBL. 
     
     
         8 . The method of  claim 7 , wherein the presence of a mutation in a nucleic acid sequence encoding human c-CBL identifies a subject that is susceptible to treatment with a c-Met inhibitor. 
     
     
         9 . The method of  claim 7 , wherein the absence of a mutation in a nucleic acid sequence encoding human c-CBL identifies a subject that is not susceptible to treatment with a c-Met inhibitor. 
     
     
         10 . The method of  claim 7 , wherein the mutation results in an amino acid change at position S80N, H94Y, Q249E, V391I, 72515_72517delATG, W802*, R830K, A848T, L620F, P170L, S171S, L281F, L254S, or P782L. 
     
     
         11 - 16 . (canceled) 
     
     
         17 . A method of determining responsiveness of a cancer in a subject to treatment with a c-Met inhibitor, said method comprising determining whether a cancer sample from a subject comprises a mutation in a nucleic acid sequence encoding human c-CBL, wherein the mutation is located in the TKB domain, RING finger domain, proline-rich region, C-terminal region, or other domain linkage regions of c-CBL, wherein the presence of the mutated nucleic acid sequence is indicative that the cancer is responsive to treatment with the c-Met inhibitor. 
     
     
         18 - 28 . (canceled)