Objective: we aimed to investigate the mutation and expression of BRAF gene in mature T/NK cell lymphoma tissues and cell lines, explore the correlation between gene alterations and clinicopathological features and clinical outcomes of mature T/NK cell lymphoma.
Methods: Firstly, we detected common mutant sites of BRAF (locus 1 799 mutation in exon 15 and loci 463, 465 and 468 mutation in exon 11) in lymphoma Jurkat, Hut-78 and YTS cell lines, normal peripheral blood lymphocytes, different types of mature T/NK cell lymphoma and reactive hyperplasia lymph nodes by direct sequencing. Then we measured the expression of BRAF in Jurkat, Hut-78, YTS cells and normal peripheral blood lymphocytes by real time-PCR and Western-blot detection. We also used immunohistochemistry (IHC) to detect the expression of BRAF in mature T/NK cell lymphoma tissues and reactive hyperplasia lymph nodes, and to analyze the correlation between the expression of BRAF and clinocopathological features and clinical outcomes.
Results: We did not find common BRAF mutation in mature T/NK cell lymphoma tissues and cell lines, and the relatively expression of BRAF gene mRNA in normal peripheral blood lymphocytes, YTS, Hut-78 and Jurkat cells were 1.000, 5.207±0.013, 8.412±0.615 and 36.720±1.797, respectively, and protein expressions were 0.051±0.003, 0.102±0.013, 0.113±0.017 and 0.304±0.010, respectively, and the expression of BRAF in peripheral T cell lymphoma Jurkat cells was significantly higher than that of Hut-78, YTS cells and normal lymphocytes (P<0.05). Only 6 of 58 peripheral T cell lymphomas (10.3%) had positive BRAF expression, and were the subgroups of peripheral T cell lymphoma-unspecified type. The statistical data did not show any correlation between positive expression of BRAF and gender, age, clinical stage, location, lactate dehydrogenase in the 21 cases of peripheral T cell lymphoma-unspecified type (P<0.05), but the positive rate of BRAF in the effective treatment group (8.3%) was significantly lower than that of the invalid group (55.6%, P<0.05).
Conclusion: The expression of BRAF gene may become a marker of malignant biological characteristics and clinical therapeutic target of peripheral T cell lymphoma.