Frequent aberrant promoter hypermethylation of O6‐methylguanine‐DNA methyltransferase and death‐associated protein kinase genes in immunodeficiency‐related lymphomas

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Abstract
Summary. Aberrant promoter hypermethylation is a mechanism of tumour suppressor gene inactivation. We explored aberrant promoter hypermethylation of multiple genes in 88 human immunodeficiency virus (HIV)‐non Hodgkin lymphomas (NHL), 25 post‐transplant lymphoproliferative disorders (PTLD) and five common variable immunodeficiency (CVI)‐related NHL. Twenty‐six of 79 (32·9%) HIV‐NHL, eight of 14 (57·1%) PTLD and two of five (40·0%) CVI–NHL showed aberrant hypermethylation of O6‐methylguanine‐DNA methyltransferase (MGMT). Aberrant hypermethylation of death‐associated protein‐kinase (DAP‐K) occurred in 70 of 84 (83·3%) HIV–NHL, 19 of 25 (72·0%) PTLD and three of five (60·0%) CVI–NHL. These data implicate MGMT and DAP‐K hypermethylation in lymphomagenesis of immunodeficient hosts. In particular, promoter hypermethylation of DAP‐K represents the most frequent molecular alteration yet identified in immunodeficiency‐related lymphomas.