弥漫性大B细胞淋巴瘤免疫球蛋白基因重排特点及规律研究

Analysis of the Character and Regularity of the Immunoglobulin Gene-rearrangements in the Diffuse Large B-cell Lymphoma

目的探讨弥漫性大B细胞淋巴瘤(DLBCL)生发中心B细胞型(GCB)及非生发中心B细胞型(non-GCB)中Ig基因重排的特点及规律。方法采用免疫组化法检测46例DLBCL中CD10、BCL-6、MUM1表达,采用Hans免疫分型方法将DLBCL分为GCB和non-GCB;同时提取所有样本基因组DNA,利用BIOMED-2克隆分析系统进行PCR扩增Ig基因,核酸分子异源双链凝胶电泳分析基因重排情况,并以15例反应性增生病变作为阴性对照。结果46例DLBCL样本中GCB 12例、non-GCB 34例,其中45例样本扩增出Ig基因的克隆性重排条带,检测敏感性为97.8%,15例反应性增生病变均未检测到重排条带,检测特异性为100.0%。GCB和non-GCB重链IGH重排差异无统计学意义(P>0.05),但轻链IGκ-A、IGκ-B和IGλ重排差异有统计学意义(P<0.05)。结论 GCB和non-GCB的Ig基因轻链重排条带分布具有显著的特点和规律,可为病理诊断和临床应用提供更为准确的依据。

Objective To analyze the character and regularity of the immunoglobufin gene-rearrangements in center B-cell type （GCB） and the non germinal center B-cell type （non-GCB） molecular sub-type in the diffuse large B- cell lymphoma （DLBCL）. Methods The expression of CDIO, BCL-6, MUM1 in 46 cases with DLBCL were determined by immunohistochemical method, which were classified into the GCB sub-type and the non-GCB sub-type with Hans Im- mnnophenotyping method. And DNA was extracted from all the tissues. BIOMED-2 standardized clonality analysis system was adopted to analyse the immunoglobulin gene rearrangements, with 15 cases of reactive hyperplasia as the negative control. Results The 46 cases of DLBCL were classified into 12 cases of GCB and 34 cases of non-GCB, among which 45 cases （97.8%） of DLBCL samples were detected to have clonal immunoglobulin gene rearrangements and all of the 15 cases of reactive lymphoid hyperplasia tissues showed polyclonal rearrangements （100.0%）. The statistic analysis showed that there was no difference in the clonal rearrangements of the heavy chains between the GCB and the non-GCB groups （ P 〉 0. 05 ）. But there was significant difference in the clonal rearrangements of the light chains including IGK-A, IGK-B, IGk in the GCB and the non-GCB sub-types （ P 〈 0.05 ）. Conclusion The immunoglobulin gene rearrangements have prominent character and regularity in he GCB and the non-GCB subtypes, which contributes to the pathological diagnosis and clinical application.