TY - JOUR
T1 - Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America
AU - Montes-Mojarro, Ivonne A.
AU - Chen, Bo Jung
AU - Ramirez-Ibarguen, Ana F.
AU - Quezada-Fiallos, Carmen M.
AU - Pérez-Báez, Wendy B.
AU - Dueñas, Daniela
AU - Casavilca-Zambrano, Sandro
AU - Ortiz-Mayor, Marcela
AU - Rojas-Bilbao, Erica
AU - García-Rivello, Hernan
AU - Metrebian, Maria F.
AU - Narbaitz, Marina
AU - Barrionuevo, Carlos
AU - Lome-Maldonado, Carmen
AU - Bonzheim, Irina
AU - Fend, Falko
AU - Steinhilber, Julia
AU - Quintanilla-Martinez, Leticia
N1 - Funding Information:
Acknowledgements The authors would like to thank Claudia Hermann and Esther Kohler for their excellent technical assistance. IAM-M is supported by funding from the European Union’s Horizon 2020 research and innovative Programme under the Marie Sklodowska-Curie grant agreement No 675712.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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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U2 - 10.1038/s41379-019-0415-5
DO - 10.1038/s41379-019-0415-5
M3 - Article
C2 - 31822801
AN - SCOPUS:85076624821
SN - 0893-3952
VL - 33
SP - 781
EP - 791
JO - Modern Pathology
JF - Modern Pathology
IS - 5
ER -