Analysis Of Molecular Genetic Features Of Sporadic Burkitt Lymphoma In Children

Objective:To investigate the molecular genetic features and diagnostic aspects of sporadic Burkitt's lymphomas (BL) in children.Methods:Pathologic diagnosis was according to the WHO classification of tumors of haematopietic and lymphoid tissues(2008).Tissue microarray was constructed to include 56 cases of pediatric BL and 9 cases of pediatric diffuse large B-cell lymphoma,not otherwise specified (DLBCL,NOS).Immunohistochemical study (SP method) for CD10,CD44,bcl-2,bcl-6 and MUM1 was performed.Fluorescence in situ hybridization (FISH) for c-myc, bcl-2,bcl-6,IgH,c-myc/IgH and bcl-2/IgH gene were performed.Cases of pediatric BL were subclassified into three groups based on their cellular origin:the germinal center (GC)group,the late-germinal center(late-GC)group,the post-germinal center(post-GC)group.The DLBCLs were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to the expression of CD10,bcl-6 and MUM1.Results:One case had bcl-6 gene rearrangement and multicopy with the pathologic and immunophenotypic characteristics of BL,leading to a revised pathological diagnosis to B-cell lymphoma,unclassifiable,with features intermediate between Diffuse large B-cell lymphoma and Burkitt lymphoma(DLBCL/BL).Among the 55 Burkitt's lymphomas studied,expression of CD10,bcl-6,bcl-2,CD44 and MUM1 by immunohistochemistry were 98.2%(54 cases),96.4%(53 cases),0(0 case),5.5%(3 cases) and 18.2%(10 cases),respectively.In 55 cases of pediatric BL:GC group 45(81.8%)cases, late-GC group 9(16.4%)cases and post-GC group 1(1.8%)case, respectively.The results of FISH of pediatric BLs are as follows:c-myc and IgH gene rearrangement were 51(92.7%)cases and 46(83.6%)cases, respectively;c-myc/IgH gene translocation was 46(83.6%)cases;46 cases(83.6%) c-myc/IgH gene translocation along with c-myc and IgH gene rearrangement; cases(9.1%)c-myc gene rearrangement without IgH and c-myc/IgH gene abnormality;4 cases(7.3%) without c-myc,IgH or c-myc/IgH gene abnormality;No case showed bcl-2 and bcl-6 gene abnormality(100%).In the 9 cases of pediatric diffuse large B-cell lymphoma studied,6 cases belonged to GCB subtype and 3 cases belonged to non-GCB subtype.In the 9 cases of pediatric diffuse large B-cell lymphoma studied, expression of CD10,bcl-6,bcl-2,CD44 and MUM1 by immunohistochemistry were 55.6%(5 cases),55.6%(5 cases),77.8%(7 cases),66.7%(6 cases) and 22.2%(2 cases), respectively.3 cases (33.3%) showed c-myc gene rearrangement.2 cases (22.2%) showed bcl-6 gene multicopy and 9 cases had a normal status of bcl-2/IgH.The positive expression of bcl-2 and CD44 in the DLBCL and BL were 7,6 and 0,3 cases.There was statistically significant difference(P=0.000).c-myc gene rearrangement and bcl-6 gene multicopy were statistically significant difference in the DLBCL and BL(P<0.05).Conclusion:(1) Most of pediatric sporadic BLs have the c-myc gene translocation to the IgH; a few cases of BL have normal c-myc and IgH gene;(2) Fluorescence in-situ hybridization is a useful technology to distinguish BL and DLBCL by c-myc and bcl-6 gene detection.(3) A majority of pediatric sporadic BLs arise from the germinal center B cells, minority derive from the late-germinal center group and the post-germinal center group.(4) Immunohistochemical study for CD44 and bcl-2 can improve the diagnosis and differential diagnosis of BL;...