Gaidano G, Capello D, Gloghini A, Fassone L, Vivenza D, Ariatti C, Migliazza A, Saglio G, Carbone A
Division of Internal Medicine, Department of Medical Sciences, "Amedeo Avogadro" University of Eastern Piedmont, via Solaroli 17, 28100 Novara, Italy.
Haematologica. 1999 Jul;84(7):582-8.
Knowledge regarding the molecular pathogenesis and histogenesis of gastrointestinal mucosa-associated lymphoid tissue non-Hodgkin's lymphomas (MALT-NHL) is limited. Mutations of BCL-6, a zinc finger transcription factor implicated in lymphoid development, occur frequently in lymphomas and represent a histogenetic marker of B-cell transit through the germinal center. The distribution of BCL-6 mutations in gastrointestinal MALT-NHL was analyzed in this study.
This study was based on 26 gastrointestinal MALT-NHL, including 16 cases of low grade histology and 10 cases of high grade histology. Mutations of BCL-6 were investigated by a combination of polymerase chain reaction-single strand conformation polymorphism and DNA direct sequencing analysis.
Mutations of BCL-6 occurred in 6/10 high grade MALT-NHL, whereas they were absent from all low grade cases tested (n = 16; p = 0.001). MALT-NHL harboring BCL-6 mutations included 5 cases of gastric MALT-NHL and 1 case of jejunal MALT-NHL. Mutations were predominantly represented by single nucleotide substitutions which were multiple in most cases. All sequence alterations were unique to individual cases of gastrointestinal MALT-NHL.
Mutations of BCL-6 occur frequently in high grade gastrointestinal MALT-NHL and display characteristics similar to those of BCL-6 mutations harbored by other B-cell lymphomas. The association of high grade MALT-NHL with BCL-6 mutations corroborates their histogenetic derivation from germinal center-related B-cells and may be of potential pathogenetic relevance for these disorders.
关于胃肠道黏膜相关淋巴组织非霍奇金淋巴瘤（MALT-NHL）的分子发病机制和组织发生学的知识有限。BCL-6是一种与淋巴发育相关的锌指转录因子，其突变在淋巴瘤中频繁发生，代表B细胞通过生发中心的组织发生学标志物。本研究分析了BCL-6突变在胃肠道MALT-NHL中的分布情况。
本研究基于26例胃肠道MALT-NHL，其中包括16例低级别组织学类型和10例高级别组织学类型。通过聚合酶链反应-单链构象多态性和DNA直接测序分析相结合的方法研究BCL-6突变情况。
10例高级别MALT-NHL中有6例发生BCL-6突变，而所有检测的低级别病例（n = 16）均未出现该突变（p = 0.001）。携带BCL-6突变的MALT-NHL包括5例胃MALT-NHL和1例空肠MALT-NHL。突变主要表现为单核苷酸替换，大多数情况下为多个替换。所有序列改变均为胃肠道MALT-NHL个别病例所特有。
BCL-6突变在高级别胃肠道MALT-NHL中频繁发生，且显示出与其他B细胞淋巴瘤所携带的BCL-6突变相似的特征。高级别MALT-NHL与BCL-6突变的关联证实了它们在组织发生学上源自生发中心相关B细胞，并且可能与这些疾病的潜在发病机制相关。
