BIOMARKERS FOR NON-HODGKIN LYMPHOMAS AND USES THEREOF
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 . A method of identifying a subject as having B-cell non-Hodgkin lymphoma (NHL), the method comprising testing a sample from the subject for a mutation in one or more biomarkers listed in Table 1, wherein the presence of the mutation identifies the subject as having B-cell NHL.
2 . The method of claim 1 , wherein testing the sample comprises detecting one or more mutations in a nucleic acid coding for one or more biomarkers listed in Table 1.
3 . The method of claim 1 , wherein testing the sample comprises detecting one or more mutations in a polypeptide coding for one or more biomarkers listed in Table 1.
4 . The method of claim 1 , wherein the sample is a tumour sample from a subject suspected of having B-cell non-Hodgkin lymphoma.
5 . The method of claim 1 , wherein the mutation is a somatic mutation.
6 . The method of claim 1 , wherein the one or more biomarkers comprise a histone modifying gene.
7 . The method of claim 1 , wherein the histone modifying gene is MLL2, MEF2B, CREBBP, EP300, EZH2 or H3K27.
8 . The method of claim 1 , wherein the one or more biomarkers are selected from FOXO1, CCND3, BTG2 and B2M.
9 . The method of claim 1 , wherein the one or more biomarkers are selected from EZH2, TNFRS14, CREBBP, BCL10, BTG1, GNA13, SGK1, MLL2 and MEF2B.
10 . The method of claim 9 , wherein the one or more biomarkers are selected from BTG1, GNA13, SGK1, MLL2 and MEF2B.
11 . The method of claim 1 , wherein the one or more biomarkers is CD79B or MYD88.
12 . The method of claim 1 , wherein the mutation is listed in Table 3.
13 . The method of claim 1 , wherein the biomarker is MLL2.
14 . The method of claim 13 , wherein the mutation is listed in Table 6.
15 . The method of claim 1 , wherein the biomarker is MEF2B.
16 . The method of claim 15 , wherein the mutation is listed in Table 7.
17 . The method of claim 15 , wherein the mutation is at amino acid position K4, Y69, N81 or D83 of a MEF2B polypeptide.
18 . The method of claim 1 , further comprising testing the sample for mutations in BCL2 or TP53.
19 . The method of claim 1 , comprising testing the sample for a mutation in 2 or more, 3 or more, 4 or more, or 5 or more biomarkers listed in Table 1.
20 . A method of classifying a subject suspected of having B-cell non-Hodgkin lymphoma (NHL) comprising testing a sample from the subject for a mutation in one or more biomarkers selected from MEF2B, SGK1, GNA13, and TNFRS14, wherein subjects that have a mutation in the one or more biomarkers are classified as having germinal centre B-cell (GCB) diffuse large B cell lymphoma (DLBCL).
21 . The method of claim 20 , further comprising testing the sample for a mutation in BCL2, TP53 or EZH2.
22 . A method of classifying a subject suspected of having B-cell non-Hodgkin lymphoma (NHL) comprising testing a sample from the subject for a mutation in MYD88 or CD79B, wherein subjects that have a mutation in MYD88 or CD79B are classified as having activated B-cell (ABC) diffuse large B cell lymphoma (DLBCL).
23 . The method of claim 20 , further comprising selecting a treatment for the subject based on the classification of the sample as GCB DLBCL.
24 . The method of claim 23 , wherein the sample is classified as GCB DLBCL and the treatment that is selected comprises administration of a histone deacetylase (HDAC) inhibitor-class drug.
25 . The method of claim 20 , wherein the sample is a tumour sample.
26 . The method of claim 20 , wherein the mutation is listed in Table 3, Table 6, or Table 7.
27 .- 30 . (canceled)