Biomarkers for Non-Hodgkin Lymphomas and Uses Thereof

Abstract

The disclosure provides a method of identifying a subject as having B-cell non-Hodgkin lymphoma (NHL) such as testing a sample from a subject for a mutation in one or more biomarkers. Also described are methods for classifying or monitoring a subject having, or suspected of having, B-cell non-Hodgkin lymphoma comprising testing the sample for a mutation in one or more biomarkers.

1 . An isolated nucleic acid molecule encoding an EZH2 protein with a mutation at position Y641 with respect to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule is a cDNA or an mRNA. 
     
     
         3 . The isolated nucleic acid molecule of  claim 2 , wherein the nucleic acid molecule has at least 90% sequence identity to SEQ ID NO: 2. 
     
     
         4 . The isolated nucleic acid molecule of  claim 1 , wherein the mutation at position Y641 is selected from Y641N, Y641H, Y641F, Y641S and Y641C. 
     
     
         5 . The isolated nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule comprises a nucleic acid sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 3) 
                 
                     
                   AT GAA TTC ATC TCA GAA AAC TGT GGA G; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   AT GAA TTC ATC TCA GAA CAC TGT GGA G; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   AT GAA TTC ATC TCA GAA TTC TGT GGA G; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   AT GAA TTC ATC TCA GAA TCC TGT GGA G; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (Y641C; SEQ ID NO: 7) 
                 
                     
                   AT GAA TTC ATC TCA GAA TGC TGT GGA G. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         6 . An isolated EZH2 protein with a mutation at position Y641 with respect to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         7 . The isolated EZH2 protein of  claim 6 , wherein the protein has at least 90% sequence identity to SEQ ID NO: 1. 
     
     
         8 . The isolated EZH2 protein of  claim 6 , wherein the mutation at position Y641 is selected from Y641N, Y641H, Y641F, Y641S and Y641C. 
     
     
         9 . An antibody that selectively binds to the EZH2 protein of  claim 6 . 
     
     
         10 . A method for identifying a subject as having B-cell non-Hodgkin lymphoma (NHL), the method comprising testing a sample from the subject for a mutation in EZH2 corresponding to a mutation at position Y641 with respect to the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         11 . The method of  claim 10 , wherein the presence of the Y641 mutation in the sample identifies the subject as having follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). 
     
     
         12 . The method of  claim 10 , wherein the mutation at position Y641 is Y641N, Y641H, Y641F, Y641S or Y641C. 
     
     
         13 . The method of  claim 10 , wherein testing the sample comprises detecting a nucleic acid molecule encoding for the Y641 mutation. 
     
     
         14 . The method of  claim 10 , wherein testing the sample comprises detecting a polypeptide encoding for the Y641 mutation. 
     
     
         15 . The method of  claim 10 , wherein the sample is a tumour sample. 
     
     
         16 . The method of  claim 10 , wherein the mutation is a heterozygous mutation. 
     
     
         17 . The method of  claim 10 , further comprising selecting a treatment for the subject based on the presence of the Y641 mutation. 
     
     
         18 . The method of  claim 17 , wherein a subject with the Y641 mutation is selected for treatment with an EZH2 inhibitor. 
     
     
         19 . The method of  claim 18 , further comprising treating the subject with an EZH2 inhibitor. 
     
     
         20 . A method of selecting treatment for a subject with B-cell non-Hodgkin lymphoma (NHL), the method comprising:
 a. testing a sample from the subject for a mutation in EZH2 corresponding to a mutation at position Y641 with respect to the amino acid sequence set forth in SEQ ID NO: 1; and   b. selecting a treatment for the subject based on the presence of the mutation at position Y641, wherein a subject with the mutation at position Y641 is selected for treatment with an EZH2 inhibitor.