Ntrk2 fusions

Abstract

The invention provides to NTRK (“Neurotrophic Tyrosine Receptor Kinase) gene fusions, NTRK. fosion proteins, and fragments of those genes and polypeptides. The invention further provides methods of diagnosing and treating diseases or disorders associated with NTRK fusions, such as conditions mediated by aberrant NTRK expression or activity, or overexpression of

1 - 81 . (canceled) 
     
     
         82 . A compound capable of specifically inhibiting a TRIM24:NTRK2, AFAP1:NTRK2, or PAN3:NTRK2 fusion, wherein the fusion results in aberrant activity or expression of NTRK2, or overexpression NTRK2, and wherein the compound is an antibody that specifically binds to a TRIM24:NTRK2, AFAP1:NTRK2, or PAN3:NTRK2 fusion protein or an RNA inhibitor that hybridizes under stringent conditions to a TRIM24:NTRK2, AFAP1:NTRK2, or PAN3:NTRK2 gene fusion. 
     
     
         83 . The compound of  claim 82 , wherein
 (a) the antibody specifically binds to:
 (i) a fragment of SEQ ID NO:3 comprising at least amino acids 665-674 of SEQ ID NO:3; 
 (ii) a fragment of SEQ ID NO:4 comprising at least amino acids 665-674 of SEQ ID NO:4; 
 (iii) a fragment of SEQ ID NO:6 comprising at least amino acids 544-553 of SEQ ID NO:6; or 
 (iv) a fragment of SEQ ID NO:8 comprising at least amino acids 138-147 of SEQ ID NO:8; and 
   (b) the RNA inhibitor hybridizes under stringent conditions to:
 (i) a fragment of SEQ ID NO:1 comprising at least nucleotides 2010-2019 of SEQ ID NO:1; 
 (ii) a fragment of SEQ ID NO:2 comprising at least nucleotides 2000-2009 of SEQ ID NO:2; 
 (iii) a fragment of SEQ ID NO:5 comprising at least nucleotides 1641-1650 of SEQ ID NO:5; or 
 (iv) a fragment of SEQ ID NO:7 comprising at least nucleotides 426-435 of SEQ ID NO:7. 
   
     
     
         84 . A method for detecting the presence of an NTRK2 fusion selected from an AFAP1:NTRK2 gene fusion, a PAN3:NTRK2 gene fusion, a TRIM24:NTRK2 protein fusion, an AFAP1:NTRK2 protein fusion, and a PAN3:NTRK2 protein fusion in a patient, said method comprising:
 a) contacting a biological sample from the patient with a reagent that specifically binds to the fusion junction of the NTRK2 fusion, and detecting binding between the NTRK2 fusion and the reagent; or   b) amplifying or sequencing a portion of a nucleic acid from the patient, and detecting the presence of a nucleotide sequence comprising at least the fusion junction of the NTRK2 fusion.   
     
     
         85 . The method of  claim 84 , wherein the NTRK2 fusion to be detected is an NTRK2 gene fusion that comprises SEQ ID NO:5 or 7, or a portion of SEQ ID NO:5 or 7, wherein the portion encodes a polypeptide having NTRK2 kinase activity and comprises the fusion junction. 
     
     
         86 . The method of  claim 85 , wherein the reagent is an oligonucleotide that hybridizes to the fusion junction of the NTRK2 gene fusion under stringent conditions. 
     
     
         87 . The method of  claim 86 , wherein the oligonucleotide hybridizes under stringent conditions to
 (a) a fragment of SEQ ID NO:5 comprising at least nucleotides 1641-1650 of SEQ ID NO:5; or   (b) a fragment of SEQ ID NO:7 comprising at least nucleotides 426-435 of SEQ ID NO:7.   
     
     
         88 . The method of  claim 84 , wherein the NTRK2 fusion to be detected is an NTRK2 fusion protein that comprises SEQ ID NO:3, 4, 6, or 8, or a portion of SEQ ID NO:3, 4, 6, or 8, wherein the portion has NTRK2 kinase activity and comprises the fusion junction. 
     
     
         89 . The method of  claim 88 , wherein the reagent is an antibody that specifically binds to the NTRK2 fusion protein, but does not specifically bind to wild-type NTRK2 or wild-type TRIM24, AFAP1, or PAN3. 
     
     
         90 . The method of  claim 89 , wherein the antibody specifically binds to
 (a) a fragment of SEQ ID NO:3 comprising at least amino acids 665-674 of SEQ ID NO:3;   (b) a fragment of SEQ ID NO:4 comprising at least amino acids 665-674 of SEQ ID NO:4;   (c) a fragment of SEQ ID NO:6 comprising at least amino acids 544-553 of SEQ ID NO:6; or   (d) a fragment of SEQ ID NO:8 comprising at least amino acids 138-147 of SEQ ID NO:8.   
     
     
         91 . The method of  claim 84 , further comprising administering to the patient a therapeutically effective amount of an NTRK2 inhibitor or an NTRK2 fusion inhibitor. 
     
     
         92 . The method of  claim 84 , wherein the patient is suffering from or susceptible to a cancer. 
     
     
         93 . The method of  claim 92 , wherein the cancer is lung adenocarcinoma, low grade glioma, squamous cell carcinoma, or head and neck squamous cell carcinoma