B细胞性非霍奇金淋巴瘤中BCL-6基因5′-非编码区突变

Study of mutations in 5′-noncoding region of BCL-6 gene in B-cell non-Hodgkin′s lymphomas

目的 分析各种类型B细胞性非霍奇金淋巴瘤 (B NHL)中BCL 6基因 5′ 非编码区突变特点 ,探讨其在淋巴瘤发生中的作用。方法 应用聚合酶链反应 (PCR)、DNA直接测序方法分析 135例B NHL[包括 5 1例弥漫性大B细胞淋巴瘤 (DLBCL)、18例滤泡性淋巴瘤 (FL)、18例B小淋巴细胞性淋巴瘤 (SLL)、15例套细胞性淋巴瘤 (MCL)、7例淋巴浆细胞性淋巴瘤 (LPL)、5例Burkitt淋巴瘤、3例B淋巴母细胞性淋巴瘤 (LBL)、18例黏膜相关淋巴组织 (MALT)淋巴瘤 ],5例T NHL、10例淋巴结反应性增生 (LRH)、5例结节型淋巴细胞为主型霍奇金淋巴瘤 (NLPHL)样本BCL 6基因 5′ 非编码区突变特点。结果 BCL 6基因 5′ 非编码区突变仅见于DLBCL(结内和结外 )、FL和MALTL中 ,突变率分别为2 7 3%、2 0 7%、2 2 2 %和 2 2 2 % ,结内、结外DLBCL中BCL 6突变率差异无显著性 (P >0 0 5 )。SLL、MCL、LPL、Burkitt淋巴瘤、LBL、T NHL以及NLPHL中均未见BCL 6突变 (P <0 0 5 )。 2例LRH的生发中心细胞可见有BCL 6突变。突变频率为 0 14× 10 -2 /bp～ 0 6 8× 10 -2 /bp ;突变类型全部为碱基替换 ,其中颠换略多于转换 (P >0 0 5 )。结论 BCL 6基因 5′ 非编码区突变可作为生发中心相关B细胞性非霍奇金淋巴瘤的分子标志 。

Objective To investigate BCL-6 gene mutations in B-cell non-Hodgkin lymphomas (B-NHL) and their implications in lymphoma pathogenesis.Methods Polymerase chain reaction (PCR) and direct DNA sequencing methods were used to identify mutations in the 5′-noncoding region of BCL-6 gene in 135 cases of B-NHL, 5 cases of T-NHL, 5 cases of nodular lymphocyte predominance Hodgkin′s lymphoma (NLPHL) and 10 cases of reactive hyperplasia of lymph node.Results Mutations were identified in 6 cases of nodal DLBCL (27.3%), 4 cases of FL (22.2%), 4 cases of MALT lymphoma(22.2%), 4 cases of extranodal DLBCL(20.7%)and 2 cases of LRH(20%). No mutations were detected in T-NHL and NLPHL (P<0.05). There were no significant differences in incidences of BCL-6 gene mutations between nodal and extranodal DLBCL (P>0.05). All mutations were base substitutions and the frequency of single-base change was 0.14×10 -2 /bp～0.68×10 -2 /bp.Conclusions Mutations of the 5′non-coding region of BCL-6 gene may be involved in the pathogenesis and progression of B-NHL. Molecular demonstration of such mutations may provide a marker of lymphomas derived from the germinal center-related B cells.