Inhibitors of human EZH2 and methods of use thereof

A method for treating a cancer in a subject, comprising:

• a) providing a nucleic acid sample from a biological sample from a subject having a cancer;
• b) contacting the nucleic acid sample with at least one primer that hybridizes to a nucleic acid encoding Enhancer of Zeste Homolog 2 (EZH2), wherein the nucleic acid sample comprises at least a portion of SEQ ID NO:
• 7 or the sequence complementary to SEQ ID NO:7, wherein the nucleic acid comprises at least one mutation including a mutation at the nucleotides encoding position Tyr641 (Y641) of the EZH2 of SEQ. ID. NO:
• 1 and wherein the mutation increases EZH2 trimethylation of Lys27 of histone H3 (H3-K27);
• c) amplifying a portion of the nucleic acid molecule containing nucleotides encoding an amino acid other than tyrosine at position Y641 of EZH2;
• d) detecting the amplified nucleic acid molecule, wherein detection of an amplified nucleic acid molecule containing nucleotides encoding an amino acid other than tyrosine at position Y641 of EZH2 indicates that the subject is responsive to an inhibitor of EZH2;
• and
• e) administering a therapeutically effective amount of an EZH2 inhibitor to the subject.