Extranodal NK/T-cell lymphoma (ENKTL) and EBV-positive nodal T/NK-cell lymphoma (nodal-TNKL) are rare, aggressive lymphomas that can share overlapping clinical and pathological features but have distinct underlying biology. Understanding these differences is important for improving disease classification and informing future treatment strategies.

In this study, co-led by N2CR members Professor Ng Siok-Bian and Dr Leong Sai Mun, an international team of researchers used methylated DNA immunoprecipitation sequencing (MeDIP-seq), a genome-wide method for mapping DNA methylation, which is a process that helps regulate whether genes are switched on or off. The team uncovered strikingly different methylation patterns between the two lymphomas. ENKTL showed extensive promoter hypermethylation associated with reduced expression of tumour-suppressor and lineage-regulatory genes. In contrast, nodal-TNKL showed widespread hypomethylation associated with immune-response and antigen-presentation pathways.

The researchers also identified two epigenetically distinct groups of ENKTL. The group with higher methylated levels had greater genomic instability and poorer overall survival. These findings provide a new molecular framework for distinguishing the two lymphomas, identifying patients who may have higher-risk ENKTL and guiding future research into biology-informed treatment approaches.

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