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The Clinical Study Of The Mutation Of 5' Noncoding Region Of BCL-6 Gene And Extranodal Diffuse Large B-cell Lymphoma

Posted on:2005-03-11Degree:MasterType:Thesis
Country:ChinaCandidate:X X ChenFull Text:PDF
GTID:2144360125450343Subject:Internal Medicine
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Malignant lymphoma is a kind of tumor originating from the lymph tissue, which has high occurrence rate in China. Non-Hodgkin's lymphoma(NHL) makes up 90 percent of all malignant lymphomas and DLBCL is the most popular disease which is correlated with abnormal chromosome. BCL-6 gene is the most relevant gene. Because the 5'noncoding regulatory region of BCL-6 is found susceptible to translocation,mutation and deletion. The arrangements would result in the deregulation expression of BCL-6 gene. Some study group found the single point mutation of noncoding regulatory region of BCL-6 gene could significantly increase the transcriptional activity of BCL-6 genes. Continuous and excessive expression would destroy the structure of GC and disordered the signals of cells. Maybe it is the important mechanism of lymphogenesis of BCL-6 mutation in the progression of DLBCL. But it still debated that whether the mutation of the mutation of noncoding region of BCL-6 gene has prognosis significance. Up to now, no systemic analysis had been done about the relationship of mutation and clinical characteristic and prognosis.We did a experimental study and retrospective analysis with 44 extronodal DLBCL patients who has been diagnosed in Jilin Third Hospital and Jilin provincial people's hospital(7 tonsil DLBCL;34 gastric and intestinal DLBCL). Artiga et al found there were two hot spot between the 5' noncoding intron and first exon, ie 106-127bp and 423-443bp. The latter mutation was related with the increase expression of BCL-6. It indicated this region contains a regulatory element. The mutation of this region would change the binding ability with hypothetical BCL-6 regulatory transcriptional elements. Based on this opinion, the PCR sections of our study contains these regions(AF191831, the first base named +1).DNA was extracted from the 44 archival paraffin-bedded extranodal DLBCL cases, then PCR and directly sequence was done. Meanwhile these cases was retrospectively analysed. The WHO classification of lymphoid neoplasm proposed in 1997 was used to classify DLBCL in this study. If it was diagnosed before 1997, the samples were reinvestigated by pathologist and immunophenotypic analysis of all surface markers had been done .23 patients were man and 21 were woman. The survival time (from diagnosis to dead or last investigation) was 2-144 month. The mean survival time is 50.93 month. All patients received at least 3 course of anthraycline-based chemotherapy. The clinical stage was defined according to Ann Arbor and Mosshoff revised suggestion. Age, sex, B symptoms, LDH, Bulky tumor mass, BM, CR and clinical stage of patients were reviewed.We did statistic analysis by SAS. The Chi-square test was used to access the statistical of comparisons in different subgroup. Survival curves were plotted according to the Method of Kaplan-Meier and were statistically compared by the Log-Rank test. Cox model was used to analyze prognostic factors of patients with DLBCL. In all analysis a P-value less than 0.05 was considered significant.The consequence of sequence shows 6/44(1 tonsil, 5 gaster and intestine)cases' BCL-6 was mutated. The rate of mutation is 13.64%( tonsil 14.29%, gaster and intestine 13.51%). 3 base substitutions was occurred in 1 case and G397C is polymorphism. 1 base was deleted in 1 case. 1 base substitution was occurred in other 4 cases. Compared to western population, the mutational rate was low, but it is similar to Taiwan group and zhouxiaoyan group. Univariate and multivariate analysis indicated 8 clinical characteristic, ie age,sex,B symptom,bulky tumor mass,stage,the level of LDH,BM involvement,CR, had no significantly influence on BCL-6 mutation. The survival curve showed the survival time of DLBCL patients with or without BCL-6 mutation has no obvious difference. But there is a tendency that the survival time of mutated patients was longer than non-mutated patients(the means of survival time is 74 vs 65.02 month). According to the Cox model we found bulky tumor mass,BM ,clini...
Keywords/Search Tags:DLBCL, BCL-6 gene, mutation, prognosis
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