Mutational characteristics of extranodal NK/T-cell lymphoma analyzed in relation to clinical prognostic indices

Extranodal NK/T-cell lymphoma (ENKTL) is a malignant lymphoma that is associated with Epstein-Barr virus (EBV) infection and poor prognosis. Several clinical risk stratification tools for ENKTL patients have been developed; however, their relationship with molecular alterations of tumor is unclear. We performed panel-based next generation sequencing (NGS) on formalin-fixed paraffin-embedded tissue of 40 ENKTL patients and analyzed them with the clinicopathological features. Patients with over 60 years of age, non-nasal type, stage III-IV, and distant lymph node involvement were 14 (35.0%), 11 (27.5%), 13 (32.5%), and 11 (27.5%), respectively. EBV DNA was detected in the blood of 30 patients (75.0%). In the NGS analysis, mutations involving the JAK/STAT pathway were the most common (n = 17, 42.5%), followed by epigenetic modifier (n = 12, 30.3%), NF-κB pathway (n = 11, 27.5%), tumor suppressor (n = 10, 25.5%), and RAS/MAPK pathway (n = 9, 22.5%). Among these, alterations involving tumor suppressor (P = 0.022) and RAS/MAPK pathway (P = 0.008) were statistically significant poor prognostic factors. Tumor suppressor gene mutations were statistically significantly related to stage III-IV (P = 0.006), distant lymph node involvement (P = 0.002), and prognostic index for natural killer cell lymphoma-EBV (PINK-E) high risk group (P = 0.017). However, alterations involving RAS/MAPK pathway did not significantly correlated with PINK-E or its components. Alterations involving tumor suppressor genes and RAS/MAPK pathway are associated with poor prognosis in ENKTL patients. Tumor suppressor gene mutations are generally correlated with previously known risk factors; however, RAS/MAPK pathway alterations are not.