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Mod Pathol ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822801


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.

Rev Invest Clin ; 66(5): 399-406, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25695382


The actual standard of care of diffuse large B-cell lymphoma (DLBCL) includes rituximab in combination with chemotherapy, with response rates up to 76%. However, this treatment may not be accessible to many patients, particularly in developing countries, where most of the treatment must be paid from the pocket of patients or their families. In México, since 2011 a federal program has fully covered this treatment of patients with DLBCL. At the Instituto Nacional de Cancerología (INCan) in Mexico City, 214 new cases with this disease were treated without cost with the standard of care in 20 months. The mean age at diagnosis was 56.7 ± 15.9 (22-91). This series of cases was compared with a retrospective analysis of cases with DLBCL attended at the INCan between 2006-2009. A total of 264 cases were retrospectively analyzed. No differences were found in demographic and clinical characteristics at time of diagnosis. However a clear positive impact was found in the group that received full treatment thanks to this new social coverage by this new social security program. The follow-up and completion of treatment was 99 %. In contrast; from 264 in the retrospective group (79%) were treated, but only 29 (10.9%) were able to receive an optimal treatment, including rituximab. These differences in treatments had a clearly impact on the response rate: 66.8 vs. 50.7% global response (full treatment vs. retrospective group, respectively). These results demonstrate the importance of social programs that may accessible standard treatment options in countries with limited resources.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Acesso aos Serviços de Saúde/economia , Linfoma Difuso de Grandes Células B/patologia , Programas Nacionais de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/economia , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem