DDR2 mutations in squamous cell lung cancer
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, the method comprising:
performing an assay to determine the identity of the nucleotides at codon 768 of discoidin domain receptor 2 (DDR2) gene in a sample comprising nucleated cells from the SCC in the subject;
determining an expected amino acid translation of the determined DDR2 sequence;
comparing the expected amino acid translation with a reference amino acid, wherein the reference amino acid is a serine;
detecting the presence of an amino acid variation relative to the reference amino acid, wherein the amino acid variation is S768R; and
administering a treatment comprising dasatinib to the subject having a S768R variation in DDR2 gene.
2. The method of claim 1 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using microarray analysis.
3. The method of claim 1 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using a nucleic acid probe that specifically hybridizes with a sequence encoding a S768R mutation.
4. A method of treating a human subject diagnosed with squamous cell carcinoma (SCC) of the lung, the method comprising:
performing an assay to determine the identity of the nucleotides at codon 768 of discoidin domain receptor 2 (DDR2) gene in a sample comprising nucleated cells from the SCC in the subject;
determining an expected amino acid translation of the determined DDR2 sequence;
comparing the expected amino acid translation with a reference amino acid, wherein the reference amino acid is a serine;
detecting the presence of an amino acid variation relative to the reference amino acid, wherein the amino acid variation is S768R; and
administering a treatment comprising nilotinib to the subject having a S768R variation in DDR2 gene.
5. The method of claim 4 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using microarray analysis.
6. The method of claim 4 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using a nucleic acid probe that specifically hybridizes with a sequence encoding a S768R mutation.
7. A method of treating a human subject diagnosed with squamous cell carcinoma (SCC) of the lung, the method comprising:
performing an assay to determine the identity of the nucleotides at codon 768 of discoidin domain receptor 2 (DDR2) gene in a sample comprising nucleated cells from the SCC in the subject;
comparing the expected amino acid translation with a reference amino acid, wherein the reference amino acid is a serine;
determining an expected amino acid translation of the determined DDR2 sequence;
comparing the expected amino acid translation with a reference amino acid, wherein the reference amino acid is a serine;
detecting the presence of an amino acid variation relative to the reference amino acid, wherein the amino acid variation is S768R; and
administering a treatment comprising imatinib to the subject having a S768R variation in DDR2 gene.
8. The method of claim 7 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using microarray analysis.
9. The method of claim 7 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using a nucleic acid probe that specifically hybridizes with a sequence encoding a S768R mutation.
10. A method of treating a human subject diagnosed with squamous cell carcinoma (SCC) of the lung, the method comprising:
performing an assay to determine the identity of the nucleotides at codon 768 of discoidin domain receptor 2 (DDR2) gene in a sample comprising nucleated cells from the SCC in the subject;
determining an expected amino acid translation of the determined DDR2 sequence; comparing the expected amino acid translation with a reference amino acid, wherein the reference amino acid is a serine;
detecting the presence of an amino acid variation relative to the reference amino acid, wherein the amino acid variation is S768R; and
administering a treatment comprising ponatinib to the subject having a S768R variation in the DDR2 gene.
11. The method of claim 10 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using microarray analysis.
12. The method of claim 10 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using a nucleic acid probe that specifically hybridizes with a sequence encoding a S768R mutation.
13. A method of treating a human subject diagnosed with squamous cell carcinoma (SCC) of the lung, the method comprising:
providing a sample comprising nucleated cells from the SCC in the subject;
contacting the sample with a nucleic acid probe that specifically hybridizes with a sequence encoding a S768R mutation of discoidin domain receptor 2 (DDR2) gene under high stringency;
detecting the presence of S768R mutation in DDR2 by hybridization of the nucleic acid probe to the DDR2 gene; and
administering a treatment comprising dasatinib, nilotinib, imatinib, or ponatinib to the subject having a S768R mutation in the DDR2 gene.
14. The method of claim 13 , wherein dasatinib is administered.
15. The method of claim 13 , wherein nilotinib is administered.
16. The method of claim 13 , wherein imatinib is administered.
17. The method of claim 13 , wherein ponatinib is administered.
18. A method of treating a human subject diagnosed with squamous cell carcinoma (SCC) of the lung, the method comprising:
performing an assay to determine the identity of the nucleotides at codon 768 of discoidin domain receptor 2 (DDR2) gene in a sample comprising nucleated cells from the SCC of the subject;
determining an expected amino acid translation of the identified nucleotides at codon 768;
comparing the expected amino acid translation with a reference amino acid, wherein the reference amino acid is serine;
detecting the presence of an amino acid variation relative to the reference amino acid, wherein the amino acid variation is S768R; and
administering a treatment comprising a tyrosine kinase inhibitor (TKI) to the subject having a S768R variation in the DDR2 gene.
19. The method of claim 18 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using microarray analysis.
20. The method of claim 18 , wherein performing an assay to determine the identity of the nucleotides at codon 768 comprises using a nucleic acid probe that specifically hybridizes with a sequence encoding a S768R mutation.
21. The method of claim 18 , wherein the TKI is dasatinib.
22. The method of claim 18 , wherein the TKI is nilotinib.
23. The method of claim 18 , wherein the TKI is imatinib.
24. The method of claim 18 , wherein the TKI is ponatinib.