Molecular Profile Detail

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Profile Name EZH2 Y641S
Gene Variant Detail

EZH2 Y641S (gain of function)

Relevant Treatment Approaches EZH2 inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
EZH2 Y641S diffuse large B-cell lymphoma sensitive EZH2 inhibitor ACY-957 + GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 enhanced the sensitivity of ACY-957 treatment in DLBCL cells harboring EZH2 Y641S in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma decreased response EZH2 inhibitor DZNeP Preclinical - Cell culture Actionable In a preclinical study, treatment with DZNeP resulted in a slight increase in number of dead or sub-G1 cells and accumulation of DNA damage in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641S in culture (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma sensitive ACY-957 Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641S demonstrated sensitivity to ACY-957 in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641S melanoma predicted - sensitive EZH2 inhibitor GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 reversed transcriptional silencing in human melanoma cells harboring wild-type EZH2 Y641S in culture (PMID: 26936398). 26936398
EZH2 Y641S follicular lymphoma sensitive EZH2 inhibitor Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646S (corresponds to Y641S in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641S diffuse large B-cell lymphoma sensitive EZH2 inhibitor ACY-957 + DZNeP Preclinical Actionable In a preclinical study, DZNeP enhanced the sensitivity of ACY-957 treatment in DLBCL cells harboring EZH2 Y641S in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma sensitive Vorinostat Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641S demonstrated sensitivity to Zolinza (vorinostat) in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641S diffuse large B-cell lymphoma decreased response EZH2 inhibitor GSK126 Preclinical - Cell culture Actionable In a preclinical study, treatment with GSK126 did not alter cell-cycle progression or decrease survival in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641S in culture (PMID: 25605023). 25605023
Clinical Trial Phase Therapies Title Recruitment Status