| Autor: |
Montes-Mojarro IA; Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany., Chen BJ; Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany.; Department of Pathology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan., Ramirez-Ibarguen AF; Department of Hematology, Instituto Nacional de Cancerología, Mexico City, Mexico., Quezada-Fiallos CM; Department of Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico., Pérez-Báez WB; Department of Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico., Dueñas D; Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru., Casavilca-Zambrano S; Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru., Ortiz-Mayor M; Department of Pathology, Hospital Ángel C. Padilla, San Miguel Tucumán, Argentina., Rojas-Bilbao E; Department of Pathology, Instituto de Oncología Ángel H. Roffo, Buenos Aires, Argentina., García-Rivello H; Department of Pathology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina., Metrebian MF; Department of Pathology, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina., Narbaitz M; Department of Pathology, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina., Barrionuevo C; Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru., Lome-Maldonado C; Department of Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico., Bonzheim I; Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany., Fend F; Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany., Steinhilber J; Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany., Quintanilla-Martinez L; Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany. Leticia.Quintanilla-Fend@med.uni-tuebingen.de. |
| Abstrakt: |
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. |
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