<p class="first" id="d4202017e265">Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr
virus (EBV) associated lymphoma,
prevalent in Asia and Latin America. Studies in Asian cohorts have identified some
recurrent gene mutations in ENKTL; however, the mutational landscape of ENKTL in Latin
America is unknown. In this study, we investigated the mutational profile and EBV
strains of 71 ENKTL cases from Latin America (42 from Mexico, 17 from Peru, and 12
from Argentina) and compared it with Asian cohorts. The mutational analysis was performed
by next generation sequencing (NGS) using an Ion AmpliSeq™ custom panel covering for
the most frequently mutated genes identified in ENKTL. STAT3 was the most frequent
mutated gene (16 cases: 23%), followed by MSN (10 cases; 14%), BCOR (9 cases; 13%),
DDX3X (6 cases; 8%), TP53 (6 cases; 8%), MGA (3 cases; 4%), JAK3 (2 cases; 3%), and
STAT5B (1 case; 1%). Mutations in STAT3, BCOR, and DDX3X were nearly mutually exclusive,
suggesting different molecular pathways involved in the pathogenesis of ENKTL; whereas
mutations in MGA, MSN, and TP53 were concomitant with other mutations. Most cases
(75%) carried Type A EBV without the 30-bp LMP1 gene deletion. The overall survival
was significantly associated with serum LDH level, Eastern Cooperative Oncology Group
(ECOG) performance status, International Prognostic Index (IPI) score, and therapy
(p < 0.05), but not associated with any mutation, EBV strain or deletion in EBV
LMP1
gene. In conclusion, mutational analysis of ENKTL from Latin America reveals frequent
gene mutations leading to activation of the JAK-STAT pathway (25%), mostly STAT3.
Compared to Asian cohorts, BCOR, DDX3X and TP53 mutations were also identified but
with different frequencies. None of these mutations were associated with prognosis.
</p>