EBV-associated primary nodal T/NK-cell lymphoma shows distinct molecular signature and copy number changes.

In this study, we assessed the relationship between nodal and extranodal EBV-positive T/NK-cell lymphomas using gene expression profiling and copy number aberration analyses. We performed GEP and CNA analysis on 66 cases of EBV-associated T/NK-cell lymphoma from nodal and extranodal sites, and correlated the molecular signatures with clinicopathologic features. Three distinct molecular clusters were identified with one enriched for nodal presentation and loss of 14q11.2 (TCRA loci). TNKL with nodal presentation (N-group) was significantly associated with older age, lack of nasal involvement, and T-cell lineage compared to those with extranodal presentation (EN-group). On multivariate analysis, nodal presentation was an independent factor associated with short survival. The molecular signature of N-group compared to EN-group was characterized by upregulation of PD-L1 and T-cell related genes, including CD2 and CD8, and downregulation of CD56, consistent with the CD8+/CD56- immunophenotype. PD-L1 and CD2 protein expression levels were validated using multiplexed immunofluorescence. Interestingly, N-group was associated with 14q11.2 loss which correlated with loss of TCR loci and T-cell origin. Overall, our results suggest that TNKL with nodal presentation is distinct and deserves to be classified separately from those with extranodal presentation. Upregulation of PD-L1 indicates the possibility of anti-PD1 immunotherapy in this distinctive entity. In addition, loss of 14q11.2 m...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research