840P - Genomic landscape, immune characteristics and prognostic mutation signature of extranodal NK/T cell lymphoma, nasal type in China

Background

This study aimed to obtain a deeper understanding of the molecular mechanisms underlying extranodal NK/T-cell lymphoma, nasal type (ENKTCL) by conducting Next-Generation Sequencing (NGS) of patients with ENKTCL.

Methods

This study included patients with ENKTCL who had complete tissue NGS results from two prior prospective studies. Group 1 comprised early-stage patients, while advanced-stage or relapsed patients were classified into Group 2. R language was used to visualize the mutation data.

Results

40 out of 98 patients with ENKTCL from two prospective clinical trials were included. Group 1 comprised 67.5% (n=27) of the patients, while group 2 accounted for 32.5% (n=13). Mutations in KLRC2 (29.6%), CIITA (25.9%), KLRC1 (25.9%), ITK (18.5%) were exclusively observed in group 1, with KLRC2 mutations occurring significantly more frequently in group 1 than group 2 (P = 0.037). KMT2D and TP53 exhibited the highest mutation rates and displayed different amino acid alterations in the two groups. The top KEGG pathway enriched by mutated genes was non-small cell lung cancer in group 1, and hepatitis B pathway in group 2. Patients with JAK3 wild-type exhibited remarkably improved PFS and OS rates than those with JAK3 mutations (P = 0.003, P = 0.033). Improved OS was also observed in patients with BCOR wild-type, although no significantly difference was found in PFS (P = 0.049, P = 0.172). Patients with PD-L1-positive expression had a significantly longer OS compared to those with PD-L1-negative expression (P = 0.037). Patients with PD-L1 expression < 50% were more likely to have BCOR mutations (41.7% vs. 0%, P = 0.012) and JAK3 gene mutations (33.3% vs. 0%, P = 0.033) than those with PD-L1 expression ≥ 50%.

Conclusions

The present study has, for the first time, explored disparities in mutation rates, mutation sites, and associated pathways among patients with early-stage versus advanced-stage/relapsed ENKTCL. JAK3 mutations, BCOR mutations, and PD-L1-negative expression were associated with poor prognosis of ENKTCL. Patients with PD-L1 expression < 50% were more likely to have BCOR mutations and JAK3 mutations than those with PD-L1 expression ≥50%.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.