Epigenetic aberrations in natural killer/T-cell lymphoma: diagnostic, prognostic and therapeutic implications

Abstract

Natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that usually presents in the upper aerodigestive tract. This malignancy shows substantial geographic variability in incidence, and is characterized by Epstein-Barr virus (EBV) infections. Epigenetic aberrations may dysregulate the expression of genes involved in different hallmarks of cancer. A growing body of evidence underscores the importance of epigenetic aberrations in the pathogenesis of NKTCL. Promoter hypermethylation is a common epigenetic mechanism for the inactivation of tumour suppressor genes. Several epigenetically silenced tumour suppressor candidates (e.g. PRDM1, BIM) were identified in this aggressive cancer using locus-specific and genome-wide promoter methylation analyses. Importantly, genes involved in epigenetic modifications were identified to be mutated (e.g. KMT2D) or methylated (e.g. TET2) in NKTCL patients, which may contribute to pathogenesis through global alterations in chromatin states. Cancer-associated microRNAs, some of which are expressed by EBV, and long noncoding RNAs have been observed to be dysregulated in NKTCL. This review focuses on studies investigating epigenetic aberrations in NKTCL to bolster our overall understanding of the role of these abnormalities in disease pathobiology. We also discuss the potential of these epigenetic aberrations to improve diagnosis and prognosis as well as reveal novel targets of therapy for NKTCL.