Aims Intravascular NK/T-cell lymphoma (IVNKTCL) is a rare disease, which is characterised by exclusive growth of large cells within the lumen of small vessels, Epstein–Barr virus infection and somatic mutations in epigenetic regulator genes. Here, we elucidate the transcriptomic complexity of IVNKTCL.

Methods IVNKTCL cases were retrieved from a single-centre cohort of 25 intravascular lymphomas. RNA-seq and whole exome sequencing (WES) were performed to analyse transcriptomic abnormalities and mutations in splicing factors.

Results Approximately 88% of the total reads from the RNA-seq were considered exonic, while the remaining reads (12%) were mapped to intronic or intergenic regions. We detected 28,941 alternative splicing events, some of which would produce abnormal proteins rarely found in normal cells. The detected events also included tumour-specific splicing alterations in oncogenes and tumour suppressors (e.g., HRAS, MDM2 and VEGFA). WES identified premature termination mutations or copy number losses in a total of 15 splicing regulator genes, including SF3B5, SRSF12 and TNPO3.

Conclusions This study raises the possibility that IVNKTCL may be driven by multiple complex regulatory loops, including non-exonic expression and aberrant splicing, in addition to defects in epigenetic regulation.