The pattern of EZH2 mutations is particularly complex, as EZH2 variants can be both gain (GOF) as well as loss of function (LOF), with GOF mutations, such as EZH2-Y646X, frequently found in lymphoid malignancies and, in particular, in non-Hodgkin lymphoma (120) and solid, non-hematological tumors and LOF typically found in myeloid malignancies. Here, EZH2 is linked to hematopoietic and lymphoid cell neoplasm.