Department of Pathology, Medical University of Vienna, Vienna, Austria.
Genes Chromosomes Cancer. 2013 Jan;52(1):33-43. doi: 10.1002/gcc.22004. Epub 2012 Sep 11.
Nodal marginal zone lymphoma (NMZL) is a primary nodal B-cell lymphoma that shares morphological and immunophenotypic characteristics with extranodal and splenic marginal zone lymphoma. Data on altered genes and signaling pathways are scarce in this rare tumor entity. To gain further insights into the genetic background of NMZL, seven cases were investigated by microarray analysis, G-banding, and FISH. Chromosomal imbalances were observed in 3/7 cases (43%) with gains of chromosome arms 1q, 8q, and 12q being the most frequent findings. Furthermore, we identified a translocation t(11;14)(q23;q32) involving IGH and DDX6. Chromosomal walking, expression analysis, siRNA-mediated gene knockdown and a yeast two hybrid screen were performed for further characterization of the translocation in vitro. In siRNA experiments, DDX6 appeared not to be involved in NF-κB activation as frequently observed for genes promoting lymphomagenesis but was found to interfere with the expression of BCL6 and BCL2 in an NF-κB independent manner. In conclusion, we identified several unbalanced aberrations and a t(11;14) involving IGH and DDX6 providing evidence for a contribution of DDX6 to lymphomagenesis by deregulation of BCL6 in NMZL.
结外边缘区淋巴瘤（NMZL）是一种原发于淋巴结的 B 细胞淋巴瘤，其形态学和免疫表型特征与结外和脾脏边缘区淋巴瘤相似。在这种罕见的肿瘤实体中，关于改变的基因和信号通路的数据很少。为了进一步了解 NMZL 的遗传背景，我们通过微阵列分析、G 带和 FISH 对 7 例 NMZL 进行了研究。在 3/7 例（43%）中观察到染色体不平衡，最常见的发现是 1q、8q 和 12q 染色体臂的获得。此外，我们鉴定了一个涉及 IGH 和 DDX6 的易位 t(11;14)(q23;q32)。为了进一步在体外对易位进行特征描述，进行了染色体步移、表达分析、siRNA 介导的基因敲低和酵母双杂交筛选。在 siRNA 实验中，DDX6 似乎不像促进淋巴瘤发生的基因那样频繁地参与 NF-κB 的激活，但被发现以 NF-κB 不依赖的方式干扰 BCL6 和 BCL2 的表达。总之，我们鉴定了几个不平衡的异常和一个涉及 IGH 和 DDX6 的易位，这表明 DDX6 通过调节 NMZL 中的 BCL6 参与了淋巴瘤的发生。
