INHIBITORS OF EZH2 AND METHODS OF USE THEREOF

1 . A method, comprising administering a therapeutically effective amount of an inhibitor of Enhancer of Zeste Homolog 2 (EZH2) sufficient to treat a cancer to a subject in need thereof, wherein the cancer is characterized by at least one mutation in one or more sequences encoding a gene or gene product listed in Tables 1-5, and/or FIGS. 1 - 3 .

2 - 8 . (canceled)

9 . The method of claim 1 , wherein the method further comprises detecting the at least one mutation in the subject.

10 . The method of claim 9 , wherein the detecting comprises subjecting a sample obtained from the subject to a sequence analysis assay.

11 . (canceled)

12 . The method of claim 10 , wherein the detecting comprises obtaining a sample from the subject.

13 . The method of claim 12 , wherein the sample is a tumor sample or a sample that comprises a cancer cell.

14 . The method of claim 12 , wherein the sample is a sample comprising ctDNA.

15 . The method of claim 1 , wherein the inhibitor of EZH2 is

(tazemetostat), or a pharmaceutically-acceptable salt thereof.

16 - 25 . (canceled)

26 . The method of claim 1 , wherein the at least one mutation comprises a MYD88 and/or STAT6A mutation.

27 . The method of claim 1 , wherein the cancer does not have a MYC and/or a HIST1H1E mutation.

28 . The method of claim 1 , wherein the cancer (a) has a MYD88 gain-of-function or a STAT6A loss-of-function mutation, and (b) has neither a MYC nor a HIST1H1E mutation.

29 . The method of claim 1 , wherein the cancer (a) has a MYD88 L273 mutation or a STAT6A loss-of-function mutation, (b) has neither a MYC nor a HIST1H1E mutation, and (c) does not have an EZH2 gain-of-function mutation.

30 - 31 . (canceled)

32 . The method of claim 1 , wherein the cancer is B-cell lymphoma.

33 - 34 . (canceled)

35 . The method of claim 1 , wherein the cancer is follicular lymphoma.

36 . A method, comprising selecting a subject having cancer for treatment with an EZH2 inhibitor based on the presence of at least one mutation associated with a positive response to such treatment in the subject and/or based on the absence of at least one mutation associated with no response or with a negative response to such treatment in the subject.

37 . The method of claim 36 , wherein the at least one mutation associated with a positive response comprise

(a) an EZH2 gain-of-function mutation or a MYD88 gain-of-function mutation; and,

(b) a STAT6 loss-of-function mutation.

38 . The method of claim 36 , wherein the at least one mutation associated with no response or with a negative response comprise

(a) a MYC mutation;

(b) a TP53 mutation; and/or,

(c) a HIST1H1E mutation.

39 . The method of claim 36 , wherein the method comprises detecting the at least one mutation associated with a positive response and/or the at least one mutation associated with no response or a negative response in a sample obtained from the subject.

40 . The method of claim 36 , wherein the method comprises selecting the subject for treatment with the EZH2 inhibitor based on the subject (a) having either an EZH2 or a MYD88 gain-of-function mutation, or a STAT6A loss-of-function mutation; and (b) having neither a MYC mutation, nor a TP53 mutation, nor a HIST1H1E mutation.

41 . The method of claim 36 , wherein the method comprises selecting the subject for treatment with the EZH2 inhibitor based on the subject

(a) having a MYD88 L273 mutation or a STAT6A mutation; and,

(b) having neither a MYC mutation, nor a TP53 mutation, nor a HIST1H1E mutation.

42 - 45 . (canceled)

46 . A method, comprising selecting a subject having cancer for treatment with an EZH2 inhibitor based on the presence of a mutation profile in the subject that matches a mutation profile of a patient exhibiting a complete or partial response or stable disease in any of Tables 1-5 or Figures 1-3.

47 - 92 . (canceled)