Array‐based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non‐CNS diffuse large B‐cell lymphomas

Primary lymphomas of the central nervous system (PCNSL) are diffuse large B‐cell lymphomas (DLBCLs) confined to the central nervous system (CNS). We here performed array‐based DNA methylation analyses of 26 PCNSL and 78 DLBCL and validated our findings in an independent dataset. We identified 2847 CpGs differentially methylated between PCNSL and non‐CNS‐DLBCL. Neither a supervised analysis using these CpGs nor application of 3 CpG classifiers selected for class separation unambiguously separated PCNSL from non‐CNS‐DLBCL. Remarkably, 6/78 non‐CNS‐DLBCL consistently segregated with PCNSL, which displayed molecular features typical for PCNSL. Our findings suggest that a subset of non‐CNS‐DLBCL exists which molecularly resembles PCNSL.