Molecular Profile Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Profile Name EZH2 Y641N
Gene Variant Detail

EZH2 Y641N (gain of function)

Relevant Treatment Approaches EZH2 inhibitor

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
EZH2 Y641N diffuse large B-cell lymphoma predicted - sensitive EZH2 inhibitor DZNeP Preclinical - Cell culture Actionable In a preclinical study, DZNeP treatment resulted in an increase in the number of dead or sub-G1 cells and increased DNA damage in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 25605023). 25605023
EZH2 Y641N diffuse large B-cell lymphoma sensitive Vorinostat Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641N demonstrated sensitivity to Zolinza (vorinostat) in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641N melanoma predicted - sensitive EZH2 inhibitor GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited H3K27 trimethylation and reversed transcriptional silencing in human melanoma cells harboring EZH2 Y641N in culture (PMID: 26936398). 26936398
EZH2 Y641N diffuse large B-cell lymphoma sensitive EZH2 inhibitor UNC1999 Preclinical Actionable In a preclinical study, UNC1999 treatment reduced H3K27me3 levels, decreased proliferation, and increased cell death in diffuse large B-cell lymphoma cells harboring an EZH2 Y641N mutation in cell culture (PMID: 23614352). 23614352
EZH2 Y641N diffuse large B-cell lymphoma no benefit EZH2 inhibitor GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 alone did not alter cell-cycle progression in survival in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 25605023). 25605023
EZH2 Y641N diffuse large B-cell lymphoma sensitive ACY-957 Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641N demonstrated sensitivity to ACY-957 in culture, resulting in increased levels of H3K27ac and cell cycle arrest (PMID: 25605023). 25605023
EZH2 Y641N 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 Y641N in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
EZH2 Y641N diffuse large B-cell lymphoma sensitive EZH2 inhibitor EED226 + EI1 Preclinical - Cell culture Actionable In a preclinical study, EED226 and EI1 synergistically inhibited cell proliferation in a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N in culture (PMID: 28135235). 28135235
EZH2 Y641N diffuse large B-cell lymphoma sensitive ACY-957 + Doxorubicin Preclinical Actionable In a preclinical study, DLBCL cells harboring EZH2 Y641N treated with the combination of ACY-957 and Adriamycin (doxorubicin) resulted in a greater sensitivity to cell death compared to treatment with either agent alone (PMID: 25605023). 25605023
EZH2 Y641N 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 Y646N (corresponds to Y641N in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641N diffuse large B-cell lymphoma sensitive EED226 Preclinical - Cell line xenograft Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring EZH2 Y641N demonstrated sensitivity to EED226, resulting in inhibition of cell proliferation in culture and delayed tumor growth and tumor regression in a cell line xenograft model (PMID: 28135235). 28135235
EZH2 Y641N 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 Y641N in culture, resulting in increased cell death and elevated levels of H3K27ac (PMID: 25605023). 25605023
Clinical Trial Phase Therapies Title Recruitment Status