Kosmidis Perikles, Bonzheim Irina, Dufke Claudia, Colak Sema, Hentrich Thomas, Schroeder Christopher, Bauer Peter, Adam Patrick, Fend Falko
Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany.
PLoS One. 2017 Jun 22;12(6):e0178503. doi: 10.1371/journal.pone.0178503. eCollection 2017.
Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. Furthermore, we identified N-glycosylation motifs characteristic for FL in the CDR3 region.
滤泡性淋巴瘤（FL）的遗传学特征是重排的免疫球蛋白重链（IGH）基因存在显著的克隆内多样性以及大量的细胞迁移活性（滤泡迁移）。最近，原位滤泡性肿瘤（ISFN）已被确定为FL的前驱病变，其进展为明显FL的风险较低，其特征是免疫组化显示BCL2强阳性、t(14;18)+克隆性B细胞聚集于反应性淋巴结的生发中心。ISFN中重排的IGH基因正在进行的体细胞超突变程度以及滤泡间迁移情况尚不清楚。在本研究中，我们对一例累及多个淋巴结的纯ISFN病例的克隆进化和细胞迁移模式进行了深入分析。通过激光显微切割和下一代测序（NGS），我们记录了重排的IGH基因显著的克隆内多样性以及同一淋巴结生发中心之间以及不同淋巴结之间广泛的滤泡间迁移。此外，我们在互补决定区3（CDR3）区域鉴定出了FL特有的N-糖基化基序。
