Menter Thomas, Juskevicius Darius, Alikian Mary, Steiger Juerg, Dirnhofer Stephan, Tzankov Alexandar, Naresh Kikkeri N
Department of Cellular and Molecular Pathology, Hammersmith Hospital Campus, Imperial College Healthcare NHS Trust, London, UK.
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Br J Haematol. 2017 Jul;178(1):48-56. doi: 10.1111/bjh.14633. Epub 2017 Apr 17.
It is currently unclear whether post-transplant diffuse large B-cell lymphomas (PT-DLBCL) display a similar genomic landscape as DLBCL in immunocompetent patients (IC-DLBCL). We investigated 50 post-transplant lymphoproliferative disorders (PTLDs) including 37 PT-DLBCL samples for somatic mutations frequently observed in IC-DLBCL. Targeted Next Generation Sequencing (NGS) using the Ion Torrent platform and a customized panel of 68 genes was performed on genomic DNA. Non-tumoural tissue was sequenced to exclude germline variants in cases where available. A control cohort of 76 IC-DLBCL was available for comparative analyses. In comparison to IC-DLBCLs, PT-DLBCL showed more frequent mutations of TP53 (P = 0·004), and absence of ATM and B2M mutations (P = 0·004 and P = 0·016, respectively). In comparison to IC-DLBCLs, Epstein-Barr virus (EBV) PT-DLBCL had fewer mutated genes (P = 0·007) and particularly fewer mutations in nuclear factor-κB pathway-related genes (P = 0·044). TP53 mutations were more frequent in EBV PT-DLBCL as compared to IC-DLBCL (P = 0·001). Germinal centre B cell (GCB) subtype of PT-DLBCL had fewer mutations and mutated genes than GCB-IC-DLBCLs (P = 0·048 and 0·04 respectively). Polymorphic PTLD displayed fewer mutations as compared to PT-DLBCL (P = 0·001). PT-DLBCL differs from IC-DLBCL with respect to mutations in genes related to DNA damage control and immune-surveillance, and EBV association is likely to have a bearing on the mutational pattern.
目前尚不清楚移植后弥漫性大B细胞淋巴瘤（PT-DLBCL）是否与免疫功能正常患者的DLBCL（IC-DLBCL）具有相似的基因组格局。我们研究了50例移植后淋巴增殖性疾病（PTLD），包括37例PT-DLBCL样本，以寻找IC-DLBCL中常见的体细胞突变。使用Ion Torrent平台和定制的68个基因的面板对基因组DNA进行靶向新一代测序（NGS）。对非肿瘤组织进行测序，以排除可用病例中的种系变异。有76例IC-DLBCL的对照队列可用于比较分析。与IC-DLBCL相比，PT-DLBCL的TP53突变更频繁（P = 0·004），且不存在ATM和B2M突变（分别为P = 0·004和P = 0·016）。与IC-DLBCL相比，爱泼斯坦-巴尔病毒（EBV）PT-DLBCL的突变基因较少（P = 0·007），尤其是核因子-κB通路相关基因的突变较少（P = 0·044）。与IC-DLBCL相比，EBV PT-DLBCL中TP53突变更频繁（P = 0·001）。PT-DLBCL的生发中心B细胞（GCB）亚型的突变和突变基因比GCB-IC-DLBCL少（分别为P = 0·048和0·04）。多形性PTLD与PT-DLBCL相比，突变较少（P = 0·001）。PT-DLBCL在与DNA损伤控制和免疫监视相关的基因的突变方面与IC-DLBCL不同，EBV关联可能与突变模式有关。
