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Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America
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Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America
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Journal Article
Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America
2020
Overview
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, DDX3
X
and
TP53
mutations were also identified but with different frequencies. None of these mutations were associated with prognosis.
Publisher
Nature Publishing Group US,Elsevier Limited
Subject
/ 45/23
/ 45/77
/ 692/699/1541/1990/291/1621/1916
/ Adult
/ Aged
/ Epstein-Barr Virus Infections - virology
/ Female
/ Humans
/ Lymphoma
/ Lymphoma, Extranodal NK-T-Cell - genetics
/ Lymphoma, Extranodal NK-T-Cell - pathology
/ Lymphoma, Extranodal NK-T-Cell - virology
/ Male
/ Medicine
/ Mutation
/ Oncology
