bcl-6基因5＇非编码区突变与弥漫性大B细胞淋巴瘤生发中心亚型的相关性

Acquired somatic mutations in non-coding region of bcl-6 gene in germinal center-type diffuse large B-cell lymphoma

目的 分析弥漫性大B细胞淋巴瘤（DLBCL）中bcl-6基因5＇非编码区突变频率及与其生发中心B细胞（GCB）型的相关性.方法 对60例DLBCL行套式PCR检测t（14;l8）易位,并经免疫组织化学EnVision两步法进行GCB和非GCB分子分型.PCR扩增bcl-6主要突变区,测序检测突变位点.结果 60例中7例（11.7%）发生t（14;18）易位,为主要断裂点发生转位;联合免疫组织化学分析和t（14;18）易位检测,筛选出GCB型18例和非GCB型42例;5＇非编码区总突变率为20.0%（12/60）,GCB型突变率为7/18,非GCB型突变率为11.9%（5/42）;＋363和＋469位点频繁发生突变.结论 DLBCL的bcl-65＇非编码区发生突变频率较国外低,突变多发生于GCB型中.t（14;18）易位检测有助于DLBCL的分子分型.

Objective To investigate the mutation of 5＇ non-coding region of bcl-6 gene in germinal center B-cell （GCB）subtype of diffuse large B-cell lymphoma（DLBCL）. Methods t（14;18） detection and immunohistochemical staining （EnVision method） were performed in 60 cases of DLBCL, which were divided into GCB and non-GCB subtypes. Polymerase chain reaction （PCR） , single-strand conformation polymorphism and direct DNA sequencing were used to identify mutations in the 5＇ non-coding region of the bcl-6 gene. Results Seven of 60 cases showed t（14;18） translocation in the major breakpoint region. Using minimally acceptable criteria, 18 of 60 cases were probably to be germinal centre derived. Bcl-6 mutations were detected in 12 of 60 cases （20. 0%） of DLBCL, with a significantly higher frequency in the GCBsubgroups （7/18） than in the non-GCB subgroups （11.9%, 5/42） . Bcl-6 mutations occurred most frequently in ＋ 363 and ＋ 469 sites. An association of bcl-6 mutation and GCB subgroup was obtained.Conclusions The 5＇ regulatory region of the bcl-6 gene underwent less frequent somatic hypermutation during lymphomagenesis than the results of previous reports. Bcl-6 mutation occurred mostly in the GCBsubtype and detection of t（14 ;18） seems helpful in the classification of DLBCL.