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 treating B-cell non-Hodgkin lymphoma (NHL) comprising administering to a human subject identified as having B-cell NHL a B-cell NHL treatment, wherein the subject is identified as having B-cell NHL by testing a sample from the subject for a mutation in Enhancer of Zeste Homolog 2 (EZH2), wherein the presence of the mutation identifies the subject as having B-cell NHL, wherein the mutation in EZH2 is a non-synonymous substitution of Alanine (A) at position 682 (A682) of a wild-type EZH2 protein sequence and/or a non-synonymous substitution of Alanine (A) at position 692 (A692) of a wild-type EZH2 protein sequence.
2. The method of claim 1 , wherein testing the sample comprises detecting one or more mutations in a nucleic acid coding for EZH2.
3. The method of claim 2 , wherein detecting one or more mutations in a nucleic acid coding for EZH2 comprises PCR, primer extension, a microarray assay, sequencing, line probes or any combination thereof.
4. The method of claim 1 , wherein the sample is a blood sample, a plasma sample or a tumor sample from a subject suspected of having B-cell non-Hodgkin lymphoma.
5. The method of claim 1 , wherein the sample is a blood sample, a tumor sample or a plasma sample.
6. The method of claim 1 , wherein the mutation in EZH2 is a non-synonymous substitution of Alanine (A) at position 692 (A692) of a wild-type EZH2 protein sequence, wherein the substitution mutation in EZH2 is A692V.
7. The method of claim 6 , wherein the mutation in EZH2 further comprises a non-synonymous substitution of Alanine (A) at position 682 (A682) of the wild-type EZH2 protein sequence, wherein the substitution mutation is A682G.
8. The method of claim 1 , wherein the mutation in EZH2 is a non-synonymous substitution of Alanine (A) at position 682 (A682) of a wild-type EZH2 protein sequence, wherein the substitution mutation in EZH2 is A682G.
9. The method of claim 8 , wherein the mutation in EZH2 further comprises a non-synonymous substitution of Alanine (A) at position 692 (A692) of the wild-type EZH2 protein sequence, wherein the substitution mutation is A692V.
10. The method of claim 1 , wherein testing the sample comprises detecting one or more mutations in an EZH2 polypeptide.
11. The method of claim 10 , wherein detecting one or more mutations in an EZH2 polypeptide comprises mass spectrometry, multiple reaction monitoring (MRM) mass spectrometry, product-ion monitoring (PIM) mass spectrometry, an immunoassay, a Western Blot assay, an ELISA assay, immunoprecipitation followed by sodium-dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) immunocytochemistry, protein sequencing or any combination thereof.
12. The method of claim 1 , wherein the substitution mutation is a somatic mutation.