Patent ID: 9334527
Filing Date: 2016-05-10
CPC Classification: A61K,A61P,C07D,C12Q,G01N,Y10T

Claim Text:
1. A method of treating cancer in a subject in need thereof comprising detecting the presence of a mutation in the EZH2 substrate pocket domain of SEQ ID NO: 7, in a sample from the subject, wherein said detecting comprises screening, at amino acid positions Y641, A677, and A687 of EZH2 of SEQ ID NO: 1, for the presence of at least one mutation, wherein the mutation at amino acid position Y641 is selected from the group consisting of a substitution of phenylalanine (F) for the wild type residue tyrosine (Y) at amino acid position 641 of SEQ ID NO: 1 (Y641F); a substitution of histidine (H) for the wild type residue tyrosine (Y) at amino acid position 641 of SEQ ID NO: 1 (Y641H); a substitution of asparagine (N) for the wild type residue tyrosine (Y) at amino acid position 641 of SEQ ID NO: 1 (Y641N); a substitution of serine (S) for the wild type residue tyrosine (Y) at amino acid position 641 of SEQ ID NO: 1 (Y641S); and a substitution of cysteine (C) for the wild type residue tyrosine (Y) at amino acid position 641 of SEQ ID NO: 1 (Y641C), wherein the mutation at amino acid position A677 is a substitution of glycine (G) for the wild type residue alanine (A) at amino acid position 677 of SEQ ID NO: 1 (A677G), wherein the mutation at amino acid position A687 is a substitution of valine (V) for the wild type residue alanine (A) at amino acid position 687 of SEQ ID NO: 1 (A687V), and wherein the mutation increases EZH2 trimethylation of Lys27 of histone H3 (H3-K27); and identifying the subject as a candidate for treatment with an EZH2 inhibitor based on the presence of a detected EZH2 mutation; administering a therapeutically effective amount of an EZH2 inhibitor to the identified subject, wherein the EZH2 inhibitor inhibits the conversion of H3-K27 to trimethylated H3-K27.