Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America

Ivonne A. Montes-Mojarro, Bo Jung Chen, Ana F. Ramirez-Ibarguen, Carmen M. Quezada-Fiallos, Wendy B. Pérez-Báez, Daniela Dueñas, Sandro Casavilca-Zambrano, Marcela Ortiz-Mayor, Erica Rojas-Bilbao, Hernan García-Rivello, Maria F. Metrebian, Marina Narbaitz, Carlos Barrionuevo, Carmen Lome-Maldonado, Irina Bonzheim, Falko Fend, Julia Steinhilber, Leticia Quintanilla-Martinez

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)781-791
Number of pages11
JournalModern Pathology
Issue number5
Publication statusPublished - May 1 2020

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


Dive into the research topics of 'Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America'. Together they form a unique fingerprint.

Cite this