Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
Haematologica. 2012 Apr;97(4):595-8. doi: 10.3324/haematol.2011.054080. Epub 2011 Nov 18.
The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and approximately 30% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a "global" NF-κB negative regulator, in 1 of 12 splenic marginal zone lymphomas. To investigate further whether deregulation of the NF-κB pathway plays a role in the pathogenesis of splenic marginal zone lymphoma, we screened several NF-κB regulators for genetic changes by PCR and sequencing. Somatic mutations were found in A20 (6/46=13%), MYD88 (6/46=13%), CARD11 (3/34=8.8%), but not in CD79A, CD79B and ABIN1. Interestingly, these genetic changes are largely mutually exclusive from each other and MYD88 mutation was also mutually exclusive from 7q deletion. These results strongly suggest that deregulation of the TLR (toll like receptor) and BCR (B-cell receptor) signaling pathway may play an important role in the pathogenesis of splenic marginal zone lymphoma.
脾脏边缘区淋巴瘤的遗传学和发病机制尚不清楚。该淋巴瘤缺乏染色体易位，约 30%的病例存在 7q 缺失，但缺失的靶基因尚不清楚。最近的一项研究表明，在 12 例脾脏边缘区淋巴瘤中，有 1 例存在 A20（一种“全局”NF-κB 负调节剂）失活。为了进一步研究 NF-κB 通路的失调是否在脾脏边缘区淋巴瘤的发病机制中起作用，我们通过 PCR 和测序筛选了几种 NF-κB 调节剂的遗传变化。在 A20（46 例中有 6 例=13%）、MYD88（46 例中有 6 例=13%）、CARD11（34 例中有 3 例=8.8%）中发现了体细胞突变，但在 CD79A、CD79B 和 ABIN1 中未发现。有趣的是，这些遗传变化在很大程度上是相互排斥的，而 MYD88 突变也与 7q 缺失相互排斥。这些结果强烈表明，TLR（toll 样受体）和 BCR（B 细胞受体）信号通路的失调可能在脾脏边缘区淋巴瘤的发病机制中起重要作用。
