This meta-analysis aims to concisely summarize the genetic landscape of splenic, nodal and extranodal marginal zone lymphomas (MZL) in the dura mater, salivary glands, thyroid, ocular adnexa, lung, stomach and skin with respect to somatic variants. A systematic PubMed search for sequencing studies of MZL was executed. All somatic mutations of the organs mentioned above were combined, uniformly annotated, and a dataset containing 25 publications comprising 6016 variants from 1663 patients was created. In splenic MZL, KLF2 (18%, 103/567) and NOTCH2 (16%, 118/725) were the most frequently mutated genes. Pulmonary and nodal MZL displayed recurrent mutations in chromatin-modifier-encoding genes, especially KMT2D (25%, 13/51, and 20%, 20/98, respectively). In contrast, ocular adnexal, gastric, and dura mater MZL had mutations in genes encoding for NF-κB pathway compounds, in particular TNFAIP3, with 39% (113/293), 15% (8/55), and 45% (5/11), respectively. Cutaneous MZL frequently had FAS mutations (63%, 24/38), while MZL of the thyroid had a higher prevalence for TET2 variants (61%, 11/18). Finally, TBL1XR1 (24%, 14/58) was the most commonly mutated gene in MZL of the salivary glands. Mutations of distinct genes show origin-preferential distribution among nodal and splenic MZL as well as extranodal MZL at/from different anatomic locations. Recognition of such mutational distribution patterns may help assigning MZL origin in difficult cases and possibly pave the way for novel more tailored treatment concepts.

这项荟萃分析旨在简明总结硬脑膜、唾液腺、甲状腺、眼附属器、肺、胃和皮肤中的脾、淋巴结和结外边缘区淋巴瘤 (MZL) 的体细胞变异的遗传图谱。对 MZL 测序研究进行了系统的 PubMed 检索。将上述器官的所有体细胞突变进行组合、统一注释，并创建了包含 25 篇出版物的数据集，其中包含来自 1663 名患者的 6016 个变异。在脾 MZL 中， KLF2 (18%, 103/567) 和NOTCH2 (16%, 118/725) 是最常见的突变基因。肺和结节 MZL 在染色质修饰符编码基因中显示出反复突变，尤其是KMT2D （分别为 25%、13/51 和 20%、20/98）。相比之下，眼附属器、胃和硬脑膜 MZL 的 NF-κB 通路化合物编码基因发生突变，特别是TNFAIP3，分别为 39% (113/293)、15% (8/55) 和 45% (5)。 /11），分别。皮肤 MZL 经常发生FAS突变 (63%, 24/38)，而甲状腺 MZL 的TET2变异患病率较高 (61%, 11/18)。最后， TBL1XR1 (24%, 14/58) 是唾液腺 MZL 中最常见的突变基因。不同基因的突变显示出在不同解剖位置的结节和脾脏 MZL 以及结外 MZL 之间的起源优先分布。识别这种突变分布模式可能有助于在困难病例中确定 MZL 起源，并可能为新颖的、更有针对性的治疗概念铺平道路。