DDR2 Mutations in Squamous Cell Lung Cancer

Abstract

Methods for treating patients with squamous cell lung cancer, including detecting the presence of mutations in the discoidin domain receptor 2 (DDR2) gene.

1 . A method of treating a human subject diagnosed with squamous cell carcinoma (SCC) of the lung, wherein the subject has a sequence in a discoidin domain receptor 2 (DDR2) gene encoding at least one amino acid variation relative to a reference amino acid sequence, and wherein the at least one amino acid variation is L63V, I120M, D125Y, G253C, G505S, C580Y, T765P, G774V, or G774E, the method comprising administering a treatment comprising a tyrosine kinase inhibitor (TKI). 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the subject is human and the reference amino acid sequence comprises SEQ ID NO: 1. 
     
     
         4 . The method of  claim 1 , wherein the reference sequence is obtained from non-cancerous cells of the same subject. 
     
     
         5 .- 7 . (canceled) 
     
     
         8 . The method of  claim 1 , comprising determining a nucleic acid sequence of a coding region of a discoidin domain receptor 2 (DDR2) gene. 
     
     
         9 . The method of  claim 1 , wherein the at least one amino acid variation results in a decrease in expression levels, half-life, or kinase activity of the DDR2 protein. 
     
     
         10 . The method of  claim 1 , wherein the TKI is dasatinib, nilotinib, imatinib, or ponatinib. 
     
     
         11 . The method of  claim 10 , wherein the TKI is dasatinib. 
     
     
         12 .- 20 . (canceled) 
     
     
         21 . The method of  claim 1 , further comprising identifying the subject as having at least one of said amino acid variations relative to the reference amino acid sequence. 
     
     
         22 . The method of  claim 21 , wherein identifying the subject comprises performing an assay to determine a nucleic acid sequence of all or part of a DDR2 gene in a sample comprising nucleated cells from a SCC in the subject, wherein the assay comprises contacting the DDR2 gene with a nucleic acid probe that specifically hybridizes with a sequence encoding at least one amino acid variation relative to a reference amino acid sequence, and wherein the at least one amino acid variation is L63V, I120M, D125Y, G253C, G505S, C580Y, T765P, G774V, or G774E; and detecting in the sample the nucleic acid sequence encoding at least one amino acid variation of L63V, I120M, D125Y, G253C, G505S, C580Y, T765P, G774E, or G774V in the DDR2 gene.