DDR2 mutations in squamous cell lung cancer

Patent metadata

Field	Value
Publication number	US-9499856-B2
Application number	US-201313875079-A
Country	US
Kind code	B2
Filing date	May 1, 2013
Priority date	Apr 2, 2012
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

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

First claim

What is claimed is:

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.

Assignees

• Broad Inst Inc
• The Board Inst Inc
• Dana Farber Cancer Inst Inc

Inventors

• Meyerson Matthew
• Hammerman Peter
• Ramos Alexis

Classifications

• C12Q1/68 Primary

  involving nucleic acids · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title