ABSTRACT
@# Objective: To analyze the mutation of target genes in extranodal natural killer/T-cell lymphoma (ENKTL) by using nextgeneration sequencing, and to explore its relationship with prognosis and clinical characteristics, as to provide evidence for the pathogenesis, clinical diagnosis and targeted therapy of ENKTL. Methods: According to previous literature reports, the genes whose mutations can affect the development of lymphoma were selected as the target genes for this study. 29 patients with ENKTL, who were newly diagnosed at the Fourth Hospital of Hebei Medical University from August 2010 to October 2018, were selected for this study. The mutation of 9 target genes in the specimen was detected by thenext-generationsequencingtechnology.Therelationshipsamongclinicalfeatures,diseaseprognosisandmutationofthetargetgeneswereanalyzedbySPSS21.0statisticalsoftware.Results： ：Ninetargetgenes were were screened. AT-rich interactive-domain 1A(ARID1A) gene showed the highest mutation rate in ENKTL (10 cases, 34.48%) followedbylysinemethyltransferase2D(KMT2D)gene(31.03%)andtumorprotein P53 (TP53) gene (24.13%). Kaplan-Meier survival analysis showed that the overall survival of ENKTL patients with KMT2D gene wild type was significantly better than patients with KMT2D gene mutation (P=0.006). The KMT2D gene mutation was found to besignificantlyrelatedtoclinicalstage,CRP,albumin,lymphocyte count and Ki67 expression in ENKTL patients (all P<0.05). COX regression analysis showed that KMT2D gene mutation was an independent adverse prognostic factor (P<0.05). Conclusion: The KMT2D gene has a high mutant frequency in ENKTL and is associated with patients’prognosis, suggesting that KMT2D gene plays an important role in the initiation and development of ENKTL. It could be used as a clinical therapeutic target for ENKTL.
ABSTRACT
@# Objective: To investigate the correlations between single nucleotide polymorphisms (SNPs) in the D-loop of mitochondrial DNA (mtDNA) and the disease risk as well as the prognosis of diffuse large B cell lymphoma (DLBCL). Methods: Blood samples from 108 DLBCL patients treated at the Department of Hematology of the Fourth Hospital of Heibei Medical University during July, 1991 and July 2012 were collected for this study; in addition, blood samples from 159 healthy controls during the same period were also collected. DNA was extracted according to the standard protocols for PCR amplification and SNP locus genotype analyses. The risk of D-loop SNPs was investigated by case-control study. Results: The minor alleles of nucleotides 73A/G, 263A/G, 315C/C insert were associated with a decreased risk for DLBCL. The minor allele of the nucleotides 200G/Awas associated with an increased risk for DLBCL. To further evaluate the predictive function of D-loop SNPs in DLBCL patients, five SNP sites were identified by Log-Rank test that with statistically significant prediction value of DLBCL survival in a univariate analysis. In a multivariate analysis, allele 16304 was identified as an independent predictor of DLBCL prognosis. The survival time of DLBCL patients with 16304C was significantly shorter than that of patients with 16304T (RR=0.513, 95% CI=0.266-0.989, P<0.05). Conclusion: The analysis of D-loop SNPs in mtDNA can help identifying the occurrence risks and poor prognosis subtypes of DLBCL.